Trial Outcomes & Findings for Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer (NCT NCT00045032)

NCT ID: NCT00045032

Last Updated: 2017-04-27

Results Overview

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an Independent Data Monitoring Committee (IDMC) in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 5099 participants
• Primary outcome timeframe: From Baseline until time of event (median of 1 year)
• Results posted on: 2017-04-27

Participant Flow

After the release of initial study results, participants in the Observation Arm without disease recurrence were given the opportunity to cross over to receive 1 or 2 years of adjuvant Herceptin. Efficacy analyses were still performed according to original randomization.

Participant milestones

Measure	Observation Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Overall Study STARTED	1697	1702	1700
Overall Study Crossover to Adjuvant Herceptin	888	0	0
Overall Study COMPLETED	834	994	974
Overall Study NOT COMPLETED	863	708	726

Reasons for withdrawal

Measure	Observation Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 milligrams per kilogram (mg/kg) via intravenous (IV) infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Overall Study Adverse Event/Intercurrent Illness	2	2	7
Overall Study Death	22	24	17
Overall Study Insufficient Therapeutic Response	542	437	445
Overall Study Violation of Selection Criteria at Entry	3	6	6
Overall Study Other Protocol Violation	2	0	1
Overall Study Refused/Did Not Cooperate/Withdrew	142	93	84
Overall Study Failure to Return	57	62	61
Overall Study Other	93	84	105

Baseline Characteristics

Herceptin (Trastuzumab) in Treating Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Primary Breast Cancer

Baseline characteristics by cohort

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Total n=5099 Participants Total of all reporting groups
Age, Continuous	49.2 years STANDARD_DEVIATION 10.08 • n=93 Participants	49.0 years STANDARD_DEVIATION 10.06 • n=4 Participants	49.2 years STANDARD_DEVIATION 10.09 • n=27 Participants	49.1 years STANDARD_DEVIATION 10.08 • n=483 Participants
Sex: Female, Male Female	1697 Participants n=93 Participants	1702 Participants n=4 Participants	1700 Participants n=27 Participants	5099 Participants n=483 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants

PRIMARY outcome

Timeframe: From Baseline until time of event (median of 1 year)

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an Independent Data Monitoring Committee (IDMC) in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Disease-Free Survival (DFS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up	12.9 percentage of participants	7.5 percentage of participants	—

PRIMARY outcome

Timeframe: From Baseline until time of event (median of 1 year)

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1694 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DFS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up	13.0 percentage of participants	7.6 percentage of participants	—

PRIMARY outcome

Timeframe: Year 2

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95 percent (%) confidence interval (CI) were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up	78.18 percentage of participants Interval 75.0 to 81.0	85.80 percentage of participants Interval 83.0 to 89.0	—

PRIMARY outcome

Timeframe: Year 2

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1694 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up	73.60 percentage of participants Interval 70.0 to 77.0	87.50 percentage of participants Interval 85.0 to 90.0	—

PRIMARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DFS Events Compared to Observation: 8-Year Median Follow-Up	33.6 percentage of participants	27.7 percentage of participants	27.8 percentage of participants

PRIMARY outcome

Timeframe: Year 3

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up	75.2 percentage of participants Interval 73.1 to 77.3	81.3 percentage of participants Interval 79.4 to 83.2	83.5 percentage of participants Interval 81.7 to 85.3

PRIMARY outcome

Timeframe: Year 5

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up	70.0 percentage of participants Interval 67.8 to 72.3	75.9 percentage of participants Interval 73.8 to 78.0	76.5 percentage of participants Interval 74.4 to 78.5

PRIMARY outcome

Timeframe: Year 7

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up	66.0 percentage of participants Interval 63.6 to 68.3	72.4 percentage of participants Interval 70.2 to 74.6	72.5 percentage of participants Interval 70.4 to 74.7

PRIMARY outcome

Timeframe: Year 8

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up	64.8 percentage of participants Interval 62.4 to 67.2	71.2 percentage of participants Interval 69.0 to 73.4	71.0 percentage of participants Interval 68.7 to 73.2

PRIMARY outcome

Timeframe: From Baseline until time of event (maximum of 10 years)

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DFS Events Compared to Observation: 10-Year Maximum Follow-Up	35.8 percentage of participants	29.7 percentage of participants	30.5 percentage of participants

PRIMARY outcome

Timeframe: Year 3

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 3 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	75.2 percentage of participants Interval 73.1 to 77.3	81.3 percentage of participants Interval 79.4 to 83.2	83.4 percentage of participants Interval 81.6 to 85.2

PRIMARY outcome

Timeframe: Year 5

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 5 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	70.0 percentage of participants Interval 67.8 to 72.2	75.9 percentage of participants Interval 73.8 to 78.0	76.4 percentage of participants Interval 74.4 to 78.5

PRIMARY outcome

Timeframe: Year 7

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 7 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	65.8 percentage of participants Interval 63.5 to 68.2	72.4 percentage of participants Interval 70.2 to 74.5	72.5 percentage of participants Interval 70.3 to 74.7

PRIMARY outcome

Timeframe: Year 8

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 8 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	64.7 percentage of participants Interval 62.3 to 67.0	71.2 percentage of participants Interval 69.0 to 73.4	70.7 percentage of participants Interval 68.5 to 72.9

PRIMARY outcome

Timeframe: Year 9

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 9 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	63.5 percentage of participants Interval 61.2 to 65.9	70.3 percentage of participants Interval 68.1 to 72.6	69.2 percentage of participants Interval 67.0 to 71.5

PRIMARY outcome

Timeframe: Year 10

Population: FAS Population

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate at Year 10 According to Kaplan-Meier Analysis Compared to Observation: 10-Year Maximum Follow-Up	62.5 percentage of participants Interval 60.1 to 64.8	69.3 percentage of participants Interval 67.0 to 71.5	68.5 percentage of participants Interval 66.2 to 70.7

SECONDARY outcome

Timeframe: From Baseline until time of event (maximum of 10 years)

Population: FAS Population 1-Year Herceptin Versus 2-Year Herceptin (1Y2Y): Participants without a DFS event and still under follow-up at the pre-defined landmark of 366 days after randomization, analyzed when intent-to-treat principle was applied for comparison of 1 year versus 2 years of Herceptin.

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants with at least one DFS event was reported.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DFS Events in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up	25.8 percentage of participants	26.6 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8, 9, 10

Population: FAS Population 1Y2Y

DFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer or second non-breast malignancy other than basal or squamous carcinoma of the skin and carcinoma in situ of the cervix, or death from any cause. The percentage of participants free of DFS events (i.e., the DFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with a 10-year maximum follow-up for DFS events.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 3	86.7 percentage of participants Interval 85.0 to 88.4	89.0 percentage of participants Interval 87.4 to 90.6	—
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 5	81.0 percentage of participants Interval 79.0 to 82.9	81.6 percentage of participants Interval 79.6 to 83.5	—
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 7	77.2 percentage of participants Interval 75.1 to 79.3	77.4 percentage of participants Interval 75.3 to 79.5	—
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 8	75.9 percentage of participants Interval 73.8 to 78.1	75.5 percentage of participants Interval 73.3 to 77.7	—
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 9	75.0 percentage of participants Interval 72.8 to 77.2	73.9 percentage of participants Interval 71.7 to 76.1	—
DFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 10-Year Maximum Follow-Up Year 10	73.9 percentage of participants Interval 71.7 to 76.1	73.1 percentage of participants Interval 70.8 to 75.3	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 1 year)

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Overall Survival (OS) Events in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up	2.4 percentage of participants	1.8 percentage of participants	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 1 year)

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

OS events referred to death from any cause. The percentage of participants who died was reported. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1694 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With OS Events in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up	2.2 percentage of participants	1.4 percentage of participants	—

SECONDARY outcome

Timeframe: Year 2

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 1-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed by the Sponsor in 2006 following database cleaning. The analysis of the Herceptin 2-Year Arm against the Observation Arm was performed for an IDMC in 2005 at a time the Sponsor was blinded. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
OS Rate According to Kaplan-Meier Analysis in Herceptin 1-Year Arm Compared to Observation: 1-Year Median Follow-Up	94.98 percentage of participants Interval 93.0 to 97.0	95.88 percentage of participants Interval 94.0 to 98.0	—

SECONDARY outcome

Timeframe: Year 2

Population: FAS Population. The "Number of Participants Analyzed" reflects the number with data for the endpoint.

OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 1-year median follow-up analysis. The analysis of the Herceptin 2-Year Arm against the Observation Arm after 1-year median follow-up, as reported below, was performed for an IDMC in 2005 at a time the Sponsor was blinded. The analysis of the Herceptin 1-Year Arm against the Observation Arm was performed by the Sponsor in 2006 following database cleaning. Therefore, these data are reported under a separate Outcome Measure.

Outcome measures

Measure	Observation Arm n=1693 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1694 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
OS Rate According to Kaplan-Meier Analysis in Herceptin 2-Year Arm Compared to Observation: 1-Year Median Follow-Up	94.39 percentage of participants Interval 92.0 to 97.0	97.28 percentage of participants Interval 96.0 to 98.0	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

OS events referred to death from any cause. The percentage of participants who died was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With OS Events Compared to Observation: 8-Year Median Follow-Up	20.6 percentage of participants	16.3 percentage of participants	16.1 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population

OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3	90.7 percentage of participants Interval 89.3 to 92.1	92.7 percentage of participants Interval 91.5 to 94.0	94.4 percentage of participants Interval 93.3 to 95.6
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5	84.5 percentage of participants Interval 82.8 to 86.3	86.9 percentage of participants Interval 85.2 to 88.5	88.7 percentage of participants Interval 87.2 to 90.3
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7	79.5 percentage of participants Interval 77.5 to 81.5	83.9 percentage of participants Interval 82.1 to 85.7	84.6 percentage of participants Interval 82.9 to 86.4
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8	77.4 percentage of participants Interval 75.2 to 79.5	82.7 percentage of participants Interval 80.8 to 84.6	82.4 percentage of participants Interval 80.4 to 84.3

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 11 years)

Population: FAS Population

OS events referred to death from any cause. The percentage of participants who died was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With OS Events Compared to Observation: 11-Year Median Follow-Up	23.9 percentage of participants	18.8 percentage of participants	18.4 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 9, 10, 11, 12

Population: FAS Population

OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 3	90.7 percentage of participants Interval 89.3 to 92.1	92.7 percentage of participants Interval 91.5 to 94.0	94.4 percentage of participants Interval 93.3 to 95.6
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 5	84.5 percentage of participants Interval 82.8 to 86.3	86.9 percentage of participants Interval 85.2 to 88.5	88.7 percentage of participants Interval 87.2 to 90.3
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 7	79.4 percentage of participants Interval 77.4 to 81.4	83.8 percentage of participants Interval 82.0 to 85.6	84.7 percentage of participants Interval 82.9 to 86.4
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 9	76.5 percentage of participants Interval 74.4 to 78.6	81.9 percentage of participants Interval 80.0 to 83.8	81.8 percentage of participants Interval 80.0 to 83.7
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 10	75.0 percentage of participants Interval 72.9 to 77.2	80.7 percentage of participants Interval 78.8 to 82.6	81.0 percentage of participants Interval 79.0 to 82.9
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 11	73.7 percentage of participants Interval 71.5 to 76.0	80.0 percentage of participants Interval 78.1 to 82.0	80.3 percentage of participants Interval 78.3 to 82.3
OS Rate According to Kaplan-Meier Analysis Compared to Observation: 11-Year Median Follow-Up Year 12	72.9 percentage of participants Interval 70.4 to 75.3	79.4 percentage of participants Interval 77.3 to 81.5	79.5 percentage of participants Interval 77.4 to 81.7

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 11 years)

Population: FAS Population 1Y2Y

OS events referred to death from any cause. The percentage of participants who died was reported.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With OS Events in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up	14.7 percentage of participants	14.9 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 9, 10, 11, 12

Population: FAS Population 1Y2Y

OS events referred to death from any cause. The percentage of participants alive (i.e., the OS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the final analysis with an 11-year median follow-up for OS events.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 3	96.5 percentage of participants Interval 95.6 to 97.4	97.4 percentage of participants Interval 96.6 to 98.2	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 5	91.4 percentage of participants Interval 90.0 to 92.8	92.6 percentage of participants Interval 91.2 to 93.9	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 7	88.6 percentage of participants Interval 87.0 to 90.2	88.7 percentage of participants Interval 87.1 to 90.3	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 9	86.7 percentage of participants Interval 85.0 to 88.5	85.9 percentage of participants Interval 84.2 to 87.7	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 10	85.4 percentage of participants Interval 83.6 to 87.2	85.1 percentage of participants Interval 83.3 to 86.9	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 11	84.7 percentage of participants Interval 82.9 to 86.6	84.4 percentage of participants Interval 82.5 to 86.2	—
OS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 11-Year Median Follow-Up Year 12	84.1 percentage of participants Interval 82.1 to 86.1	83.6 percentage of participants Interval 81.5 to 85.6	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Recurrence-Free Survival (RFS) Events Compared to Observation: 8-Year Median Follow-Up	29.8 percentage of participants	23.4 percentage of participants	22.6 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population

RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3	76.4 percentage of participants Interval 74.3 to 78.4	82.7 percentage of participants Interval 80.9 to 84.6	86.0 percentage of participants Interval 84.3 to 87.6
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5	71.9 percentage of participants Interval 69.7 to 74.1	78.4 percentage of participants Interval 76.4 to 80.4	79.9 percentage of participants Interval 77.9 to 81.9
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7	69.0 percentage of participants Interval 66.7 to 71.3	75.7 percentage of participants Interval 73.6 to 77.8	76.7 percentage of participants Interval 74.6 to 78.8
RFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8	68.4 percentage of participants Interval 66.1 to 70.7	75.1 percentage of participants Interval 72.9 to 77.2	75.8 percentage of participants Interval 73.6 to 77.9

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population 1Y2Y

RFS events included local, regional, or distant tumor recurrence. The percentage of participants with at least one RFS event was reported.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With RFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up	19.7 percentage of participants	18.8 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population 1Y2Y

RFS events included local, regional, or distant tumor recurrence. The percentage of participants free of RFS events (i.e., the RFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 3	87.7 percentage of participants Interval 86.0 to 89.3	90.9 percentage of participants Interval 89.4 to 92.3	—
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 5	83.1 percentage of participants Interval 81.2 to 85.0	84.5 percentage of participants Interval 82.7 to 86.4	—
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 7	80.2 percentage of participants Interval 78.2 to 82.3	81.3 percentage of participants Interval 79.3 to 83.2	—
RFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 8	79.6 percentage of participants Interval 77.5 to 81.6	80.3 percentage of participants Interval 78.2 to 82.3	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Distant Disease-Free Survival (DDFS) Events Compared to Observation: 8-Year Median Follow-Up	28.8 percentage of participants	23.4 percentage of participants	23.2 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population

DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3	78.6 percentage of participants Interval 76.6 to 80.6	84.4 percentage of participants Interval 82.7 to 86.2	85.9 percentage of participants Interval 84.2 to 87.6
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5	74.2 percentage of participants Interval 72.1 to 76.4	79.6 percentage of participants Interval 77.6 to 81.6	80.2 percentage of participants Interval 78.2 to 82.1
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7	70.8 percentage of participants Interval 68.6 to 73.1	76.7 percentage of participants Interval 74.6 to 78.8	76.7 percentage of participants Interval 74.6 to 78.8
DDFS Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8	69.6 percentage of participants Interval 67.3 to 71.9	75.5 percentage of participants Interval 73.4 to 77.6	75.6 percentage of participants Interval 73.4 to 77.7

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population 1Y2Y

DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants with at least one DDFS event was reported.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DDFS Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up	19.5 percentage of participants	19.5 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population 1Y2Y

DDFS events included distant tumor recurrence, second primary cancer, or contralateral breast cancer. The percentage of participants free of DDFS events (i.e., the DDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 3	89.4 percentage of participants Interval 87.9 to 91.0	90.8 percentage of participants Interval 89.4 to 92.2	—
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 5	84.5 percentage of participants Interval 82.7 to 86.3	84.7 percentage of participants Interval 82.9 to 86.5	—
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 7	81.4 percentage of participants Interval 79.5 to 83.4	81.1 percentage of participants Interval 79.1 to 83.1	—
DDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 8	80.1 percentage of participants Interval 78.1 to 82.2	79.9 percentage of participants Interval 77.8 to 81.9	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Tumor Recurrence (TR) Compared to Observation: 8-Year Median Follow-Up	29.8 percentage of participants	23.4 percentage of participants	22.6 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population

The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3	76.5 percentage of participants Interval 74.4 to 78.5	82.8 percentage of participants Interval 81.0 to 84.6	86.1 percentage of participants Interval 84.4 to 87.7
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5	72.1 percentage of participants Interval 69.9 to 74.3	78.6 percentage of participants Interval 76.6 to 80.6	80.1 percentage of participants Interval 78.2 to 82.1
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7	69.2 percentage of participants Interval 67.0 to 71.5	75.9 percentage of participants Interval 73.9 to 78.0	77.0 percentage of participants Interval 75.0 to 79.1
TR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8	68.6 percentage of participants Interval 66.4 to 70.9	75.3 percentage of participants Interval 73.2 to 77.4	76.2 percentage of participants Interval 74.1 to 78.3

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population 1Y2Y

The percentage of participants with TR of the present breast cancer was reported. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With TR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up	19.7 percentage of participants	18.8 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population 1Y2Y

The percentage of participants without TR of the present breast cancer (i.e., the TR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. TR included local, regional, or distant tumor ignoring contralateral breast cancer and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 3	87.7 percentage of participants Interval 86.1 to 89.4	90.9 percentage of participants Interval 89.5 to 92.4	—
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 5	83.2 percentage of participants Interval 81.3 to 85.1	84.7 percentage of participants Interval 82.9 to 86.5	—
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 7	80.4 percentage of participants Interval 78.4 to 82.4	81.5 percentage of participants Interval 79.6 to 83.5	—
TR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 8	79.8 percentage of participants Interval 77.7 to 81.8	80.6 percentage of participants Interval 78.6 to 82.6	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population

The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Distant Tumor Recurrence (DTR) Compared to Observation: 8-Year Median Follow-Up	25.3 percentage of participants	19.4 percentage of participants	18.8 percentage of participants

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population

The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1697 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1702 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1700 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 3	79.8 percentage of participants Interval 77.8 to 81.7	85.9 percentage of participants Interval 84.2 to 87.6	88.1 percentage of participants Interval 86.5 to 89.6
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 5	76.5 percentage of participants Interval 74.4 to 78.5	82.1 percentage of participants Interval 80.2 to 84.0	83.4 percentage of participants Interval 81.5 to 85.2
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 7	74.0 percentage of participants Interval 71.8 to 76.1	80.1 percentage of participants Interval 78.2 to 82.1	80.7 percentage of participants Interval 78.8 to 82.6
DTR-Free Rate According to Kaplan-Meier Analysis Compared to Observation: 8-Year Median Follow-Up Year 8	73.3 percentage of participants Interval 71.1 to 75.5	79.5 percentage of participants Interval 77.5 to 81.5	80.3 percentage of participants Interval 78.3 to 82.2

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population 1Y2Y

The percentage of participants with DTR was reported. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With DTR in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up	15.5 percentage of participants	15.1 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population 1Y2Y

The percentage of participants without DTR (i.e., the DTR-free rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis. DTR included distant tumors ignoring local and regional recurrences, contralateral breast cancer, and second non-breast malignancy.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 3	90.5 percentage of participants Interval 89.0 to 91.9	92.4 percentage of participants Interval 91.1 to 93.8	—
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 5	86.7 percentage of participants Interval 85.0 to 88.4	87.5 percentage of participants Interval 85.8 to 89.2	—
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 7	84.6 percentage of participants Interval 82.8 to 86.4	84.9 percentage of participants Interval 83.1 to 86.7	—
DTR-Free Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 8	83.9 percentage of participants Interval 82.1 to 85.8	84.4 percentage of participants Interval 82.6 to 86.3	—

SECONDARY outcome

Timeframe: From Baseline until time of event (median of 8 years)

Population: FAS Population 1Y2Y. In contrast to other study endpoints, RDFS compared to the Observation Arm was not a planned endpoint according to study protocol. Only RDFS in Herceptin 1-Year Arm versus Herceptin 2-Year Arm was a planned endpoint.

RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants with at least one RDFS event was reported.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Restricted Disease-Free Survival (RDFS) Events in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up	22.2 percentage of participants	21.9 percentage of participants	—

SECONDARY outcome

Timeframe: Years 3, 5, 7, 8

Population: FAS Population 1Y2Y. In contrast to other study endpoints, RDFS compared to the Observation Arm was not a planned endpoint according to study protocol. Only RDFS in Herceptin 1-Year Arm versus Herceptin 2-Year Arm was a planned endpoint.

RDFS events included loco-regional or distant recurrence of breast cancer, development of contralateral breast cancer, or death from any cause. The percentage of participants free of RDFS events (i.e., the RDFS rate) and corresponding 95% CI were estimated by Kaplan-Meier analysis based on available data at the time of the 8-year median follow-up analysis.

Outcome measures

Measure	Observation Arm n=1552 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1553 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 5	81.9 percentage of participants Interval 79.9 to 83.8	83.0 percentage of participants Interval 81.1 to 84.9	—
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 3	87.3 percentage of participants Interval 85.6 to 89.0	89.9 percentage of participants Interval 88.4 to 91.4	—
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 7	78.5 percentage of participants Interval 76.4 to 80.6	78.9 percentage of participants Interval 76.9 to 81.0	—
RDFS Rate According to Kaplan-Meier Analysis in 1-Year Versus 2-Year Herceptin: 8-Year Median Follow-Up Year 8	77.2 percentage of participants Interval 75.1 to 79.3	77.7 percentage of participants Interval 75.5 to 79.8	—

SECONDARY outcome

Timeframe: From Baseline until time of event (maximum up to 10 years)

Population: Safety Population: All participants randomized/enrolled in the study according to actual treatment received. Hence, participants assigned to Herceptin who received no study treatment were analyzed in the Observation Arm.

Primary cardiac endpoint events included the occurrence of any of the following between randomization and new therapy for recurrent disease: symptomatic New York Heart Association (NYHA) Class III or IV congestive heart failure (CHF) confirmed by a cardiologist with a drop in left ventricular ejection fraction (LVEF) at least 10 percentage points from Baseline and to a value less than (<) 50%, and documentation of definite or probable cardiac death. Definite cardiac death included CHF, myocardial infarction, or primary arrhythmia. Probable cardiac death included unexpected sudden death within 24 hours of a cardiac event (syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. The percentage of participants with at least one primary cardiac endpoint event was reported. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.

Outcome measures

Measure	Observation Arm n=1744 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1682 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1673 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Primary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up	0.11 percentage of participants Interval 0.01 to 0.41	1.07 percentage of participants Interval 0.64 to 1.69	1.02 percentage of participants Interval 0.59 to 1.62

SECONDARY outcome

Timeframe: From Baseline until time of event (maximum up to 10 years)

Population: Safety Population

Secondary cardiac endpoint events included NYHA Class I or II CHF with a drop in LVEF measured by multiple-gated acquisition or electrocardiogram, unless the subsequent assessment of LVEF indicated a return to levels that did not meet the definition of a significant LVEF drop. A significant LVEF drop was defined as an absolute reduction of at least 10 percentage points from Baseline and to a value <50%. The percentage of participants with at least one secondary cardiac endpoint event was reported, excluding those with both a primary and secondary cardiac endpoint event. The 95% CI was calculated by the Pearson-Clopper method for a one-sample binomial.

Outcome measures

Measure	Observation Arm n=1744 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided.	Herceptin 1-Year Arm n=1682 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1673 Participants Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Percentage of Participants With Secondary Cardiac Endpoint Events Compared to Observation: 10-Year Maximum Follow-Up	0.86 percentage of participants Interval 0.48 to 1.41	4.40 percentage of participants Interval 3.47 to 5.49	7.29 percentage of participants Interval 6.09 to 8.64

Adverse Events

Observation Arm

Serious events: 143 serious events

Other events: 1076 other events

Deaths: 0 deaths

Herceptin 1-Year Arm

Serious events: 269 serious events

Other events: 1389 other events

Deaths: 0 deaths

Herceptin 2-Year Arm

Serious events: 344 serious events

Other events: 1440 other events

Deaths: 0 deaths

Serious adverse events

Measure	Observation Arm n=1744 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided. After the release of initial study results, participants in the Observation Arm were allowed to cross over to receive adjuvant Herceptin prior to disease recurrence. As such, adverse events that occurred after crossover were not included in the safety analyses for this arm.	Herceptin 1-Year Arm n=1682 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1673 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Laceration	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Nerve injury	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Patella fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Asthma	0.23% 4/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Blood and lymphatic system disorders Leukopenia	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Acute coronary syndrome	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Acute myocardial infarction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Angina pectoris	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Arrhythmia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Atrial fibrillation	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Atrial flutter	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Atrioventricular block	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Atrioventricular block complete	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Bradycardia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Cardiac arrest	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Cardiac failure	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Cardiac failure chronic	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Cardiac failure congestive	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	1.1% 19/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	1.4% 24/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Cardiomyopathy	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Coronary artery disease	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Coronary artery stenosis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Extrasystoles	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Hypertensive heart disease	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Left ventricular dysfunction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Left ventricular failure	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Myocardial infarction	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Palpitations	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Pericarditis lupus	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Sinus node dysfunction	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Supraventricular tachycardia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Tachyarrhythmia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Tachycardia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Ventricular fibrillation	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Congenital, familial and genetic disorders Dermoid cyst	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Congenital, familial and genetic disorders Odontogenic cyst	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Congenital, familial and genetic disorders Tooth hypoplasia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Congenital, familial and genetic disorders Ventricular septal defect	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Ear and labyrinth disorders Otosclerosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Ear and labyrinth disorders Vertigo	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Endocrine disorders Basedow's disease	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Endocrine disorders Goitre	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Eye disorders Cataract	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Eye disorders Eyelid ptosis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Eye disorders Glaucoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Eye disorders Retinal detachment	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Eye disorders Visual impairment	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Abdominal hernia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Abdominal pain	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Anal fissure	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Diarrhoea	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Dyspepsia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Gastritis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Haemorrhoids	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Hiatus hernia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Ileus	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Inguinal hernia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Intestinal obstruction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Large intestine polyp	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Nausea	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Oesophagitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Pancreatitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Pancreatitis acute	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Paraesthesia oral	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Vomiting	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Adverse drug reaction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Axillary pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Breast complication associated with device	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Catheter site haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Chest pain	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Chills	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Death	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Device breakage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Device dislocation	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Device failure	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Device leakage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Fat necrosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Fatigue	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Granuloma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Ill-defined disorder	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Local swelling	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Medical device complication	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Medical device pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Mucosal haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Multi-organ disorder	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Non-cardiac chest pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Pain	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Peripheral swelling	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Pyrexia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.36% 6/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Sudden death	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Cholecystitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Cholecystitis chronic	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Cholelithiasis	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Cholestasis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Hepatitis toxic	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Immune system disorders Anaphylactic reaction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Immune system disorders Anaphylactic shock	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Immune system disorders Drug hypersensitivity	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Abdominal wall abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Anal abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Appendicitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Arthritis infective	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Atypical pneumonia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Bartholin's abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Breast abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Breast cellulitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Bronchitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Catheter site cellulitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Catheter site infection	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Cellulitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.30% 5/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.30% 5/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Device related infection	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.54% 9/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.48% 8/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Device related sepsis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Diverticulitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Endocarditis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Endometritis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Erysipelas	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.48% 8/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Extradural abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Gastroenteritis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Genital infection female	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Hepatitis B	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Herpes zoster	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Infection	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Influenza	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Labyrinthitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Lower respiratory tract infection	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Lymphangitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Mastitis	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Muscle abscess	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Neutropenic sepsis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Parotitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Peritonitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Pneumonia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.30% 5/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Pneumonia bacterial	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Postoperative wound infection	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Pulmonary mycosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Pulmonary sepsis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Pyelonephritis acute	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Pneumothorax traumatic	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Rectal abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Respiratory tract infection	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Salmonellosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Salpingo-oophoritis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Soft tissue infection	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Spinal cord abscess	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Staphylococcal sepsis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Streptococcal sepsis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Tonsillitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Tuberculosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Upper respiratory tract infection	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Urinary tract infection	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Wound infection	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Acetabulum fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Alcohol poisoning	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Ankle fracture	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Concussion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Femur fracture	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Fibula fracture	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Fractured coccyx	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Hand fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Post procedural haematoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Postoperative hernia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Procedural pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Radiation pneumonitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Radius fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Rib fracture	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Scar	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Spinal column injury	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Upper limb fracture	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Wound	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Injury, poisoning and procedural complications Wound secretion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Investigations Ejection fraction decreased	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Investigations Gamma-glutamyltransferase increased	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Investigations Hepatic enzyme increased	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Metabolism and nutrition disorders Decreased appetite	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Arthritis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Muscle tightness	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Neck pain	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Osteoarthritis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Tendon disorder	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Tenosynovitis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoid cystic carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenosquamous cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Angiosarcoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign breast neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of bladder	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of skin	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder papilloma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.52% 9/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	1.6% 27/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	2.2% 36/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the gastrointestinal tract	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage 0	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage II	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal adenocarcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric adenoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hodgkin's disease	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Inflammatory myofibroblastic tumour	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive papillary breast carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipofibroma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.36% 6/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.48% 8/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.48% 8/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mantle cell lymphoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal squamous cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian adenoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paget's disease of nipple	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.17% 3/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Retro-orbital neoplasm	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second primary malignancy	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the vulva	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Undifferentiated sarcoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.42% 7/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyosarcoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulval cancer stage 0	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Brain oedema	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Carpal tunnel syndrome	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Central nervous system haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Cerebellar atrophy	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Cerebral haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Cerebral infarction	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Cerebral ischaemia	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Cerebrovascular accident	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Dementia Alzheimer's type	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Headache	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Hypoaesthesia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Ischaemic stroke	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Migraine	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Myoclonus	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Nystagmus	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Optic neuritis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Paresis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Sciatica	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Seizure	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Syncope	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Transient ischaemic attack	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Tremor	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Abortion missed	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.42% 7/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Complication of pregnancy	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Delivery	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Pregnancy, puerperium and perinatal conditions Pregnancy	0.63% 11/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	1.3% 22/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	1.7% 29/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Alcohol abuse	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Anxiety	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Completed suicide	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Delusion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Depression	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.30% 5/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Major depression	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Renal and urinary disorders Hydronephrosis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Renal and urinary disorders Nephrolithiasis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Renal and urinary disorders Urinary incontinence	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Adnexa uteri mass	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast calcifications	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast disorder	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast dysplasia	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast fibrosis	0.17% 3/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.30% 5/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast haematoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast hyperplasia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast inflammation	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.18% 3/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast mass	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast necrosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Breast pain	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Cervical polyp	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Endometrial hyperplasia	0.17% 3/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.42% 7/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Endometriosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Fibrocystic breast disease	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Genital prolapse	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Menorrhagia	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Metrorrhagia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Nipple exudate bloody	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Ovarian cyst	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Rectocele	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Uterine polyp	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Uterine prolapse	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Productive cough	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Vocal cord polyp	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Dermal cyst	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Drug eruption	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Eczema	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Erythema	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Prurigo	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Scar pain	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Skin mass	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Surgical and medical procedures Mammoplasty	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Surgical and medical procedures Nerve block	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Aortic occlusion	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Deep vein thrombosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.24% 4/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Flushing	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Haematoma	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Haemorrhage	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Hypertension	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Hypertensive crisis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Hypotension	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Jugular vein thrombosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Microangiopathy	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Subclavian vein thrombosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Thrombophlebitis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Thrombosis	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Vena cava thrombosis	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.12% 2/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.06% 1/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	0.00% 0/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population

Other adverse events

Measure	Observation Arm n=1744 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant. No Herceptin was provided. After the release of initial study results, participants in the Observation Arm were allowed to cross over to receive adjuvant Herceptin prior to disease recurrence. As such, adverse events that occurred after crossover were not included in the safety analyses for this arm.	Herceptin 1-Year Arm n=1682 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 1 year or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.	Herceptin 2-Year Arm n=1673 participants at risk Participants who completed definitive surgery and systemic adjuvant chemotherapy received a loading dose of Herceptin as 8 mg/kg via IV infusion on Day 1, followed by a maintenance dose of 6 mg/kg via IV infusion 3 weeks later and thereafter every 3 weeks for 2 years or until disease recurrence, whichever occurred first. Participants were observed for efficacy and safety until 10 years from individual randomization and for survival until 10 years after enrollment of the last participant.
Cardiac disorders Cardiac failure congestive	1.0% 18/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.6% 78/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	7.6% 127/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Cardiac disorders Palpitations	1.1% 20/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.3% 72/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.0% 84/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Diarrhoea	1.3% 22/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	9.2% 155/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	10.8% 180/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Nausea	2.1% 37/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.0% 134/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	9.4% 157/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Gastrointestinal disorders Vomiting	0.86% 15/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.6% 77/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.9% 99/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Asthenia	2.4% 42/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.1% 102/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	7.1% 119/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Chest pain	2.1% 37/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	3.7% 63/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.0% 84/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Chills	0.06% 1/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.9% 99/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	7.7% 128/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Fatigue	4.8% 83/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	11.8% 198/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	14.7% 246/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Oedema peripheral	2.8% 49/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.9% 82/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.0% 101/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
General disorders Pyrexia	0.69% 12/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.9% 116/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.7% 145/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Influenza	0.97% 17/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.6% 95/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.5% 142/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Nasopharyngitis	3.7% 65/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	11.1% 187/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	16.1% 269/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Infections and infestations Upper respiratory tract infection	1.8% 31/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	3.2% 53/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.0% 84/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Arthralgia	8.7% 152/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	13.4% 225/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	14.7% 246/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Back pain	6.1% 106/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.7% 146/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.2% 137/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Muscle spasms	0.80% 14/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.1% 69/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.4% 91/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Musculoskeletal pain	3.7% 64/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.2% 70/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.5% 92/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Myalgia	1.6% 28/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.2% 88/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.2% 104/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 74/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.8% 97/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.4% 107/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Dizziness	2.3% 40/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.9% 82/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.3% 89/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Nervous system disorders Headache	4.1% 72/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	12.0% 201/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	14.9% 250/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Depression	3.4% 59/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.2% 88/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.8% 80/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Psychiatric disorders Insomnia	2.8% 49/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.7% 96/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.5% 75/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Cough	3.6% 62/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.9% 116/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.8% 147/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 46/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.9% 83/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.9% 116/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Nail disorder	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	3.1% 52/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.0% 83/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Onychoclasis	0.11% 2/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	3.2% 53/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.9% 98/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Skin and subcutaneous tissue disorders Rash	1.4% 25/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.9% 99/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	8.1% 135/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Hot flush	7.5% 130/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	9.9% 166/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	9.5% 159/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Hypertension	3.5% 61/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	6.2% 104/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	7.7% 128/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population
Vascular disorders Lymphoedema	4.0% 70/1744 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	4.8% 81/1682 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population	5.5% 92/1673 • From Baseline until end of treatment (maximum up to 2 years) with the exception of cardiac/cardiovascular events, second primary malignancies, pregnancies, and Herceptin-related adverse events (maximum up to 10 years) Analysis Population Description: Safety Population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: global-roche-genentech-trials@gene.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER