Trial Outcomes & Findings for Surgery to Remove the Sentinel Lymph Node and Axillary Lymph Nodes After Chemotherapy in Treating Women With Stage II, Stage IIIA, or Stage IIIB Breast Cancer (NCT NCT00881361)

Last Updated: 2023-04-27

Results Overview

False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN1 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. A 2-sided Bayesian credible interval (BCI) for the true FNR was constructed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

756 participants

Primary outcome timeframe

At time of surgery

Results posted on

2023-04-27

Participant Flow

Participant milestones

Participant milestones
Measure	cN1 Cohort Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN2 Cohort Patients who were staged according to the AJCC staging system as cN2 (disease in fixed or matted axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN3 Patients (Ineligible) Patients who were staged according to the AJCC staging system as cN3.
Overall Study STARTED	707	47	2
Overall Study COMPLETED	663	38	0
Overall Study NOT COMPLETED	44	9	2

Reasons for withdrawal

Reasons for withdrawal
Measure	cN1 Cohort Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN2 Cohort Patients who were staged according to the AJCC staging system as cN2 (disease in fixed or matted axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN3 Patients (Ineligible) Patients who were staged according to the AJCC staging system as cN3.
Overall Study Terminated prior to surgery	27	7	0
Overall Study Ineligible	17	2	2

Baseline Characteristics

Surgery to Remove the Sentinel Lymph Node and Axillary Lymph Nodes After Chemotherapy in Treating Women With Stage II, Stage IIIA, or Stage IIIB Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	cN1 Cohort n=663 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN2 Cohort n=38 Participants Patients who were staged according to the AJCC staging system as cN2 (disease in fixed or matted axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Total n=701 Participants Total of all reporting groups
Age, Customized 18-39 years old	120 participants n=5 Participants	4 participants n=7 Participants	124 participants n=5 Participants
Age, Customized 40-49 years old	213 participants n=5 Participants	15 participants n=7 Participants	228 participants n=5 Participants
Age, Customized 50-59 years old	197 participants n=5 Participants	10 participants n=7 Participants	207 participants n=5 Participants
Age, Customized 60-69 years old	112 participants n=5 Participants	5 participants n=7 Participants	117 participants n=5 Participants
Age, Customized greater than 70 years old	21 participants n=5 Participants	4 participants n=7 Participants	25 participants n=5 Participants
Sex: Female, Male Female	663 Participants n=5 Participants	38 Participants n=7 Participants	701 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	663 Participants n=5 Participants	38 Participants n=7 Participants	701 Participants n=5 Participants

PRIMARY outcome

Timeframe: At time of surgery

Population: Of the cN1 Cohort patients who Started the study (see Participant Flow), only patients with residual nodal disease were included in this analysis.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=525 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN1 Breast Cancer [cN1 Cohort]	12.6 percentage of participants Interval 9.85 to 16.05	—

SECONDARY outcome

Timeframe: At time of surgery

Population: Of the cN2 Cohort patients who Started the study (see Participant Flow), only patients with residual nodal disease were included in this analysis.

False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy when at least 2 SLNs were excised in women initially presenting with biopsy-proven cN2 breast cancer, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients initially presenting with biopsy-proven cN1 breast cancer with at least one positive lymph node by SLN or ALND multiplied by 100. An interval estimate of the SLN false negative rate will be constructed using the Duffy-Santner approach.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=38 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
False Negative Rate (FNR) for Sentinel Lymph Node (SLN) Surgery After Chemotherapy When at Least 2 SLNs Were Excised in Women Initially Presenting With Biopsy-proven cN2 Breast Cancer [cN2 Cohort]	0 percentage of false-negative SLN finding Interval 0.0 to 23.2	—

SECONDARY outcome

Timeframe: At the time of surgery

False negative rate (FNR) (percentage) for sentinel lymph node (SLN) surgery after chemotherapy in women with normal AUS and at least 2 SLNs were excised, defined as the number of patients with no positive lymph nodes by SLN and with at least one positive lymph node by axillary lymph node dissection (ALND) divided by the total number of patients with at least one positive lymph node by SLN or ALND multiplied by 100.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=470 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
False-negative Rate (FNR) Under the Selection Process by Axillary Ultrasound (AUS) Status After Completion of Neoadjuvant Chemotherapy (NAC)	12.6 percentage of false-negative SLN finding Interval 9.5 to 16.3	—

SECONDARY outcome

Timeframe: At time of surgery

Population: Patients with post-chemotherapy AUS results were included in this analysis.

Node status of patients after preoperative chemotherapy, as measured by the total number of positive nodes (SLN+ALND). Patients will be classified as node positive if they were determined to have at least one positive lymph node by SLN or ALND.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=430 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious n=181 Participants Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) 0	171 Participants	47 Participants
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) 1-3	173 Participants	89 Participants
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) 4-10	42 Participants	28 Participants
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) >10	10 Participants	7 Participants
Node Status After Preoperative Chemotherapy, as Measured by the Total Number of Positive Nodes (SLN+ALND) Missing/Unknown	34 Participants	10 Participants

SECONDARY outcome

Timeframe: At the time of surgery

Population: Patients in cN1 and cN2 Cohort who had at least two SLNs excised and went on to complete ALND were included in this analysis.

Pathologic complete nodal response (pCR) rate (percentage) wherein a nodal pCR is pathologically node-negative (pN0) on the basis of SLN surgery and ALND. A 95% binomial confidence interval was constructed for the pCR rate.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=525 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious n=26 Participants Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
Pathologic Complete Nodal Response (pCR) Rate	41.0 percentage of SLN surgery/ALND Interval 36.7 to 45.3	46.1 percentage of SLN surgery/ALND Interval 26.6 to 66.6

SECONDARY outcome

Timeframe: At time of surgery

Residual cancer burden (RCB) is estimated from routine pathologic sections of the primary breast tumor site and the regional lymph nodes after the completion of neoadjuvant therapy. The calculated RCB index value can also be categorized as one of four RCB classes. The number of patients classified in the four RCB classes along with the number of patients missing this data by cohort are reported below. RCB of 0 represents a path complete response while increasing levels (I, then II, then III) indicate an increase in the 'amount' of residual disease remaining.

Outcome measures

Outcome measures
Measure	cN1 Cohort n=663 Participants Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	Post-chemotherapy AUS Suspicious n=38 Participants Patients with lymph nodes with abnormal morphology on AUS were classified as suspicious.
Residual Cancer Burden Class missing data	162 participants	6 participants
Residual Cancer Burden Class 0	182 participants	13 participants
Residual Cancer Burden Class I	33 participants	0 participants
Residual Cancer Burden Class II	136 participants	10 participants
Residual Cancer Burden Class III	150 participants	9 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 10 years

Outcome measures

Outcome data not reported

Adverse Events

cN1 Cohort

Serious events: 6 serious events

Other events: 192 other events

Deaths: 1 deaths

cN2 Cohort

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	cN1 Cohort n=676 participants at risk Patients who were staged according to the AJCC staging system as cN1 (disease in movable axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.	cN2 Cohort n=39 participants at risk Patients who were staged according to the AJCC staging system as cN2 (disease in fixed or matted axillary lymph nodes) and plan to receive or have received neoadjuvant chemotherapy are eligible. Patients undergo examination for breast and axilla lymph adenopathy and then undergo ultrasound of the axillary nodes at baseline and after completion of neoadjuvant chemotherapy. Within 12 weeks of completing neoadjuvant chemotherapy, patients undergo a mastectomy or lumpectomy (per surgeon discretion) including both sentinel lymph node surgery and axillary lymph node dissection.
Blood and lymphatic system disorders Hemoglobin decreased	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
General disorders Multi-organ failure	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
Infections and infestations Infection	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
Infections and infestations Skin infection	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
Infections and infestations Wound infection	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
Metabolism and nutrition disorders Dehydration	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.
Musculoskeletal and connective tissue disorders Upper extremity dysfunction	0.15% 1/676 • Number of events 1 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.	0.00% 0/39 • 1-2 weeks post surgery Each CTCAE term is a unique representation of a specific event used for medical documentation \& scientific analysis \& is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who started treatment \& were evaluated for AEs. Serious AE (SAE) reports may include any secondary serious/non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and are in the SAE table.

Other adverse events

Additional Information

Judy C. Boughey, MD

Mayo Clinic

Phone: 507-284-3629

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place