Trial Outcomes & Findings for Study of Estrogen Levels in Premenopausal Women Who Have Undergone Surgery for Breast Cancer and Are Receiving Triptorelin and Tamoxifen Citrate or Exemestane on Clinical Trial IBCSG 24-02 (NCT NCT00975676)

Last Updated: 2021-10-25

Results Overview

Estrogen levels (estradiol \[E2\], estrone \[E1\], and estrone sulphate \[E1S\]) were measured at the following time points for the SOFT-EST: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization. Some of these samples were not used, including un-scheduled sample, post surgery or vaginal bleeding, samples taken post early discontinuation (ED) or discontinuation of GnRH injections.

Recruitment status

COMPLETED

Study phase

Target enrollment

123 participants

Primary outcome timeframe

0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization

Results posted on

2021-10-25

Participant Flow

The SOFT-EST substudy was activated on 25 Nov 2008. Participating Centers were expected to enroll all or most patients who planned to use triptorelin as method of OFS, if randomized to receive OFS, into this substudy. The accrual goal for the substudy was 120 patients (30 T+OFS; 90 E+OFS). Enrollment of 30 patients randomly assigned to T+OFS was reached by 31 Dec 2009; enrollment of patients randomly assigned to E+OFS continued until SOFT and SOFT-EST enrollment closed on 31 Jan 2011.

Participant milestones

Participant milestones
Measure	Triptorelin Plus Tamoxifen Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years. The final analytic cohort included 109 patients from the intent to treat (ITT) population, who had ≥2 samples assayed or E+Trip=83, T+Trip=26 respectively, patients with only baseline data were excluded.	Triptorelin Plus Exemestane Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years. The final analytic cohort included 109 patients from the intent to treat (ITT) population, who had ≥2 samples assayed or E+Trip=83, T+Trip=26 respectively, patients with only baseline data were excluded.
Overall Study STARTED	32	91
Overall Study COMPLETED	26	83
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Triptorelin Plus Tamoxifen Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years. The final analytic cohort included 109 patients from the intent to treat (ITT) population, who had ≥2 samples assayed or E+Trip=83, T+Trip=26 respectively, patients with only baseline data were excluded.	Triptorelin Plus Exemestane Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years. The final analytic cohort included 109 patients from the intent to treat (ITT) population, who had ≥2 samples assayed or E+Trip=83, T+Trip=26 respectively, patients with only baseline data were excluded.
Overall Study Baseline samples only, no sample analyzed or only single sample available	6	8

Baseline Characteristics

Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Triptorelin Plus Tamoxifen n=26 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years. gas chromatography / tandem mass spectometry: Determination of estrogen levels through gas chromatography.	Triptorelin Plus Exemestane n=83 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years. gas chromatography / tandem mass spectometry: Determination of estrogen levels through gas chromatography.	Total n=109 Participants Total of all reporting groups
Age, Customized <35	0 Participants n=26 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	8 Participants n=83 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	8 Participants n=109 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.
Age, Customized 35-39	5 Participants n=26 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	10 Participants n=83 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	15 Participants n=109 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.
Age, Customized 40-44	7 Participants n=26 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	26 Participants n=83 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	33 Participants n=109 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.
Age, Customized 45-49	14 Participants n=26 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	39 Participants n=83 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.	53 Participants n=109 Participants • Patient characteristics for the analytic cohort of 109 patients according to treatment assignment.
Sex: Female, Male Female	26 Participants n=26 Participants	83 Participants n=83 Participants	109 Participants n=109 Participants
Sex: Female, Male Male	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Asian	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Black or African American	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) White	25 Participants n=26 Participants	81 Participants n=83 Participants	106 Participants n=109 Participants
Race (NIH/OMB) More than one race	0 Participants n=26 Participants	0 Participants n=83 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=26 Participants	2 Participants n=83 Participants	3 Participants n=109 Participants
Estradiol (E2), pg/mL	109.81 pg/mL STANDARD_DEVIATION 119.81 • n=26 Participants • Excludes 2 patients without baseline samples	96.55 pg/mL STANDARD_DEVIATION 151.23 • n=81 Participants • Excludes 2 patients without baseline samples	99.78 pg/mL STANDARD_DEVIATION 143.68 • n=107 Participants • Excludes 2 patients without baseline samples
Estrone (E1), pg/mL	60.27 pg/mL STANDARD_DEVIATION 52.40 • n=26 Participants • Excludes 2 patients without baseline samples	65.42 pg/mL STANDARD_DEVIATION 78.12 • n=81 Participants • Excludes 2 patients without baseline samples	64.17 pg/mL STANDARD_DEVIATION 72.52 • n=107 Participants • Excludes 2 patients without baseline samples
Estrone sulfate (E1S), pg/mL	1437.02 pg/mL STANDARD_DEVIATION 1825.06 • n=26 Participants • Excludes 2 patients without baseline samples	1371.21 pg/mL STANDARD_DEVIATION 1763.84 • n=81 Participants • Excludes 2 patients without baseline samples	1387.20 pg/mL STANDARD_DEVIATION 1770.42 • n=107 Participants • Excludes 2 patients without baseline samples
Follicle-stimulating hormone (FSH), LU/L	25.14 LU/L STANDARD_DEVIATION 29.05 • n=25 Participants • Excludes 6 patients without baseline samples	30.30 LU/L STANDARD_DEVIATION 27.37 • n=78 Participants • Excludes 6 patients without baseline samples	29.05 LU/L STANDARD_DEVIATION 27.73 • n=103 Participants • Excludes 6 patients without baseline samples
Luteinizing hormone (LH), LU/L	16.77 LU/L STANDARD_DEVIATION 16.29 • n=25 Participants • Excludes 5 patients without baseline samples	18.97 LU/L STANDARD_DEVIATION 16.12 • n=79 Participants • Excludes 5 patients without baseline samples	18.44 LU/L STANDARD_DEVIATION 16.11 • n=104 Participants • Excludes 5 patients without baseline samples

PRIMARY outcome

Timeframe: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization

Population: The final (4 years) analysis cohort (N=109) consists of all patients from the intent to treat (ITT) population (N=123) who had at least 2 samples analyzed and who received at least one GnRH analogue triptorelin injection during follow-up. Fourteen patients were excluded due to the reasons of 1) never start TE and never received GnRH (gonadotropin-releasing hormone) analogue triptorelin; 2) only baseline sample available; 3) single sample at 24 months; 4) patients without sample analyzed.

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=26 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=83 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at baseline (0 months)	109.81 pg/mL Standard Deviation 119.151	96.55 pg/mL Standard Deviation 151.235
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 3 months	4.876 pg/mL Standard Deviation 7.123	3.973 pg/mL Standard Deviation 8.439
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 6 months	3.761 pg/mL Standard Deviation 2.02	3.672 pg/mL Standard Deviation 8.006
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 12 months	4.013 pg/mL Standard Deviation 2.765	2.486 pg/mL Standard Deviation 5
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 18 months	7.306 pg/mL Standard Deviation 16.325	2.527 pg/mL Standard Deviation 6.204
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 24 months	4.453 pg/mL Standard Deviation 3.347	2.52 pg/mL Standard Deviation 6.566
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 36 months	3.704 pg/mL Standard Deviation 2.138	1.654 pg/mL Standard Deviation 2.764
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estradiol (E2) levels at 48 months	5.914 pg/mL Standard Deviation 8.959	9.073 pg/mL Standard Deviation 57.307
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at baseline (0 months)	60.27 pg/mL Standard Deviation 52.4	65.42 pg/mL Standard Deviation 78.12
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 3 months	17.8 pg/mL Standard Deviation 6.73	2.93 pg/mL Standard Deviation 3.33
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 6 months	18.66 pg/mL Standard Deviation 7.54	2.73 pg/mL Standard Deviation 3.12
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 12 months	19.05 pg/mL Standard Deviation 8.4	3.71 pg/mL Standard Deviation 6.35
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 18 months	18.64 pg/mL Standard Deviation 9.35	8.47 pg/mL Standard Deviation 33.42
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 24 months	18.96 pg/mL Standard Deviation 7.63	4.69 pg/mL Standard Deviation 9.16
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 36 months	19.49 pg/mL Standard Deviation 7.32	4.93 pg/mL Standard Deviation 9.16
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone (E1) levels at 48 months	19.14 pg/mL Standard Deviation 7.24	8.53 pg/mL Standard Deviation 35.07
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at baseline (0 months)	1437 pg/mL Standard Deviation 1825.06	1371 pg/mL Standard Deviation 1763.84
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 3 months	281.4 pg/mL Standard Deviation 183.44	56.02 pg/mL Standard Deviation 133.71
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 6 months	259 pg/mL Standard Deviation 167.23	54.7 pg/mL Standard Deviation 97.66
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 12 months	278.5 pg/mL Standard Deviation 236.38	47.31 pg/mL Standard Deviation 130.45
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 18 months	281.8 pg/mL Standard Deviation 160.6	63.52 pg/mL Standard Deviation 175.19
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 24 months	242.6 pg/mL Standard Deviation 96.75	73.56 pg/mL Standard Deviation 258.29
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 36 months	249.4 pg/mL Standard Deviation 113.27	53.27 pg/mL Standard Deviation 151.03
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy Estrone sulfate (E1S) levels at 48 months	231.1 pg/mL Standard Deviation 93.46	112 pg/mL Standard Deviation 556.81

PRIMARY outcome

Timeframe: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization

Population: Among patients randomly assigned to exemestane + triptorelin and included in the analysis cohort (N=83), the number of patients who experienced suboptimal suppression at each timepoint, with 95% exact binomial confidence intervals (CI), were reported. Two patients were excluded due to no baseline sample.

Suboptimal estrogen suppression (SES), estradiol (E2) levels greater than 2.72 pg/mL in at least 2 post-baseline samples.

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=83 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at baseline (0 months)	74 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 3 months	17 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 6 months	16 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 12 months	12 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 18 months	12 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 24 months	8 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 36 months	8 Participants	—
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression Patients with E2 > 2.72 pg/mL at 48 months	3 Participants	—

SECONDARY outcome

Timeframe: baseline (0 months), 3, 6, 12, 18, 24, 36, and 48 months from randomization

Percent (%) change of estrogen levels estradiol (E2), estrone (E1), and estrone sulphate (E1S) at each timepoint from baseline: e.g. {E2(t)-E2(0)} / E2(0)\*100, where t= 3, 6, 12, 18, 24, 36, and 48 months from randomization

Outcome measures

SECONDARY outcome

Timeframe: Four years after randomization

Population: All patients from the Intent to treat (ITT) population assigned to exemestane +triptorelin (N=83) according to suboptimal estrogen suppression (SES) with E2 \> 2.72 pg/mL (suboptimal threshold) or any vaginal bleeding \> 3 mos after triptorelin start or pregnancy

Potential predictive factors of ineffective estrogen suppression (SES) (with E2 \> 2.72 pg/mL, or any vaginal bleeding \> 3 months after triptorelin start or pregnancy) such as: age, evidence of menses at entry, BMI, chemotherapy (yes/no), and, type of chemotherapy received

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=21 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=62 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Age at randomization (years), <35	3 Participants	5 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Age at randomization (years), >=35	18 Participants	57 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Menstrual status, normal	13 Participants	24 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Menstrual status, irregular	3 Participants	11 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Menstrual status, persistent amenorrhea	5 Participants	27 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression BMI (kg/m2), normal (<25)	9 Participants	36 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression BMI (kg/m2), over weight (25-<30)	8 Participants	16 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression BMI (kg/m2), obese (>=30)	3 Participants	9 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo, no	12 Participants	25 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo, yes	9 Participants	37 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo regimen, no chemo	12 Participants	25 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo regimen, anthracycline-based	3 Participants	7 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo regimen, taxane-based	0 Participants	2 Participants
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression Prior chemo regimen, anthracycline+taxane	6 Participants	28 Participants

SECONDARY outcome

Timeframe: Baseline

The secondary analysis explored baseline estrogen levels (E2, E1, E1S) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm.

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=21 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=62 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm Baseline estradiol (E2)	80 pg/mL Interval 60.0 to 121.0	39 pg/mL Interval 6.0 to 83.0
Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm Baseline estrone (E1)	50 pg/mL Interval 26.0 to 59.0	41 pg/mL Interval 23.0 to 71.0
Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm Baseline estrone sulphate (E1S)	928 pg/mL Interval 572.0 to 1168.0	715 pg/mL Interval 302.0 to 1330.0

SECONDARY outcome

Timeframe: Baseline

The secondary analysis explored endocrine functions (FSH, LH) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm.

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=21 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=62 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm Baseline follicle-stimulating hormone (FSH)	6 IU/L Interval 5.0 to 8.0	32 IU/L Interval 10.0 to 58.0
Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm Baseline luteinizing hormone (LH)	6 IU/L Interval 4.0 to 8.0	21 IU/L Interval 7.0 to 32.0

SECONDARY outcome

Timeframe: Less than 12 months, at 12 months

Endocrine function (FSH, LH) status according to treatment assignments at 12 months using 12 month data alone or 12 month data plus earlier data (when 12 month not available)

Outcome measures

Outcome measures
Measure	Triptorelin Plus Tamoxifen n=26 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=83 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Endocrine Functions (FSH and LH) Status According to Treatment Assignments Luteinizing hormone (LH) at 12 months	0.2 IU/L Interval 0.1 to 0.4	0.1 IU/L Interval 0.1 to 0.1
Endocrine Functions (FSH and LH) Status According to Treatment Assignments Follicle-stimulating hormone (FSH) at 12 months	2.0 IU/L Interval 1.5 to 2.6	7.0 IU/L Interval 5.2 to 8.8
Endocrine Functions (FSH and LH) Status According to Treatment Assignments Follicle-stimulating hormone (FSH) at <=12 months	2.2 IU/L Interval 1.6 to 3.1	6.5 IU/L Interval 4.8 to 8.7
Endocrine Functions (FSH and LH) Status According to Treatment Assignments Luteinizing hormone (LH) at <=12 months	0.2 IU/L Interval 0.1 to 0.4	0.1 IU/L Interval 0.1 to 0.2

Adverse Events

Triptorelin Plus Tamoxifen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Triptorelin Plus Exemestane

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Head Trial Activities and Deputy Director Dr. Heidi Roschitzki-Voser Organization

International Breast Cancer Study Group (IBCSG)

Phone: +41 31 511 94 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Triptorelin Plus Tamoxifen n=26 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.	Triptorelin Plus Exemestane n=83 Participants Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 0 months (baseline)	0 percent change of estrogen levels Standard Deviation 0	0 percent change of estrogen levels Standard Deviation 0
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 3 months	-70 percent change of estrogen levels Standard Deviation 40	-76 percent change of estrogen levels Standard Deviation 75
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 6 months	-69 percent change of estrogen levels Standard Deviation 44	-82 percent change of estrogen levels Standard Deviation 62
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 12 months	-57 percent change of estrogen levels Standard Deviation 61	-83 percent change of estrogen levels Standard Deviation 47
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 18 months	-61 percent change of estrogen levels Standard Deviation 50	-85 percent change of estrogen levels Standard Deviation 37
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 24 months	-63 percent change of estrogen levels Standard Deviation 48	-79 percent change of estrogen levels Standard Deviation 61
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 36 months	-56 percent change of estrogen levels Standard Deviation 44	-86 percent change of estrogen levels Standard Deviation 33
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estradiol (E2) at 48 months	-65 percent change of estrogen levels Standard Deviation 41	-79 percent change of estrogen levels Standard Deviation 87
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 0 months (baseline)	0 percent change of estrogen levels Standard Deviation 0	0 percent change of estrogen levels Standard Deviation 0
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 3 months	-48 percent change of estrogen levels Standard Deviation 41	-90 percent change of estrogen levels Standard Deviation 18
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 6 months	-43 percent change of estrogen levels Standard Deviation 50	-90 percent change of estrogen levels Standard Deviation 19
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 12 months	-38 percent change of estrogen levels Standard Deviation 55	-81 percent change of estrogen levels Standard Deviation 61
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 18 months	-44 percent change of estrogen levels Standard Deviation 37	-75 percent change of estrogen levels Standard Deviation 86
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 24 months	-40 percent change of estrogen levels Standard Deviation 43	-84 percent change of estrogen levels Standard Deviation 33
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 36 months	-29 percent change of estrogen levels Standard Deviation 39	-82 percent change of estrogen levels Standard Deviation 35
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone (E1) at 48 months	-41 percent change of estrogen levels Standard Deviation 33	-70 percent change of estrogen levels Standard Deviation 133
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 0 months (baseline)	0 percent change of estrogen levels Standard Deviation 0	0 percent change of estrogen levels Standard Deviation 0
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 3 months	-43 percent change of estrogen levels Standard Deviation 73	-90 percent change of estrogen levels Standard Deviation 27
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 6 months	-50 percent change of estrogen levels Standard Deviation 59	-87 percent change of estrogen levels Standard Deviation 35
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 12 months	-35 percent change of estrogen levels Standard Deviation 82	-92 percent change of estrogen levels Standard Deviation 17
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 18 months	-35 percent change of estrogen levels Standard Deviation 68	-92 percent change of estrogen levels Standard Deviation 16
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 24 months	-27 percent change of estrogen levels Standard Deviation 87	-88 percent change of estrogen levels Standard Deviation 33
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 36 months	-26 percent change of estrogen levels Standard Deviation 63	-70 percent change of estrogen levels Standard Deviation 173
Comparison of Estrogen Levels at Different Time Points During Treatment Percent change from baseline of estrone sulfate (E1S) at 48 months	-36 percent change of estrogen levels Standard Deviation 66	-87 percent change of estrogen levels Standard Deviation 53