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

Study Overview
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Brief Summary
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RATIONALE: Studying samples of blood from patients with breast cancer in the laboratory may help doctors learn how well triptorelin given together with tamoxifen citrate or exemestane works in lowering estrogen levels. PURPOSE: This clinical trial is studying 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-2402.

Detailed Description
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OBJECTIVES: Primary Describe estrogen levels (estradiol [E2], estrone [E1], and estrone sulphate [E1S]) at different time points during the first 4 years of treatment with triptorelin in combination with either tamoxifen citrate or exemestane on clinical trial IBCSG-2402 in premenopausal women with resected breast cancer. Assess whether there is a suboptimally estrogen-suppressed subgroup of patients who receive exemestane. Secondary Compare estrogen levels (E2, E1, E1S) at different time points during treatment with triptorelin in combination with either tamoxifen citrate or exemestane. Examine potential predictive factors of ineffective estrogen suppression (e.g., age, chemotherapy [yes/no], type of chemotherapy received, smoking history, BMI, and evidence of menses at study entry). Investigate the predictive value of optimal estrogen suppression during the first 6 and 12 months of treatment with regard to long-term estrogen suppression (4-year period). Compare disease-free survival of suboptimally estrogen-suppressed patients treated with exemestane with that of patients with optimal suppression (exploratory analysis). Examine related endocrine function (FSH and LH) to further elucidate causes of suboptimal estrogen suppression. OUTLINE: This is a multicenter study. Blood samples are collected at baseline and at 3, 6, 12, 18, 24, 36, and 48 months for measurement of estrogen levels (estradiol [E2], estrone [E1], and estrone sulphate [E1S]) by gas chromatography-mass spectrometry and measurement of endocrine function (FSH and LH).

Official Title
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A Substudy of the IBCSG 24-02/ SOFT Trial to Investigate Estrogen Suppression for Patients Participating in Arms B and C of the IBCSG 24-02/ SOFT Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: gas chromatography / tandem mass spectometry


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed resected breast cancer Concurrent enrollment on clinical trial IBCSG-2402 (SOFT trial) required Randomized to receive triptorelin in combination with either tamoxifen citrate or exemestane Hormone receptor status: Estrogen receptor- and/or progesterone receptor-positive tumor PATIENT CHARACTERISTICS: Premenopausal PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triptorelin plus tamoxifen<br>Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years. | Other: gas chromatography / tandem mass spectometry<br>* Determination of estrogen levels through gas chromatography.<br>|
| Experimental: Triptorelin plus exemestane<br>Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years. | Other: gas chromatography / tandem mass spectometry<br>* Determination of estrogen levels through gas chromatography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization | 
| Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Suboptimal estrogen suppression (SES), estradiol (E2) levels greater than 2.72 pg/mL in at least 2 post-baseline samples. | 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Estrogen Levels at Different Time Points During Treatment | 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 | baseline (0 months), 3, 6, 12, 18, 24, 36, and 48 months from randomization | 
| Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | 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 | Four years after randomization | 
| Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | 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. | Baseline | 
| Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | 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. | Baseline | 
| Endocrine Functions (FSH and LH) Status According to Treatment Assignments | 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) | Less than 12 months, at 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer