S9630, Medroxyprogesterone in Treating Women With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: It is not yet known whether medroxyprogesterone is effective in preventing endometrial disorder in patients with breast cancer who are taking tamoxifen. PURPOSE: Randomized phase III trial to study the effectiveness of medroxyprogesterone in preventing endometrial disorder in postmenopausal women who have ductal carcinoma in situ, lobular carcinoma in situ, Paget's disease of the nipple, stage I breast cancer, or stage II breast cancer and who are taking tamoxifen.

Detailed Description
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OBJECTIVES: Compare endometrial pathologic diagnoses (proliferative changes, simple or cystic hyperplasia, complex adenomatous hyperplasia, hyperplasia with atypia, and carcinoma) in postmenopausal women with breast carcinoma treated with adjuvant tamoxifen who are randomly assigned to medroxyprogesterone acetate (MA) vs observation. Compare endometrial pathologic diagnoses (persistent endometrial hyperplasia, atypia, or carcinoma) resulting in tamoxifen discontinuation and intermittent bleeding in patients treated with these regimens. Characterize the incidence of spontaneous regression and progression of simple or cystic hyperplasia in these patients. Characterize endometrial biopsy results using different endometrial stripe width cut-off points, for cases in which the width is at least 5 mm by endovaginal ultrasound in patients receiving tamoxifen. Compare changes over time in endometrial oncogene expression (e.g., c-fos, c-jun, p53, IGF1) and receptor status in patients receiving tamoxifen with or without prior chemotherapy who are randomly assigned to MA vs observation. Describe the associations among change in gene expression, receptor status, endometrial abnormality, length of tamoxifen exposure, and prior chemotherapy in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to adjuvant chemotherapy (yes vs no), number of positive nodes (0-3 vs at least 4), and endovaginal sonogram endometrial stripe (less than 5 mm vs at least 5 mm). Patients are randomized to 1 of 2 arms. All patients receive adjuvant oral tamoxifen daily for five years. Arm I: Patients undergo observation. Arm II: Patients receive oral medroxyprogesterone acetate on days 1-14. Treatment repeats every 3 months for 5 years. Patients are followed every 6 months for 2 years and then annually thereafter. PROJECTED ACCRUAL: A total of 330 patients (165 per arm) will be accrued for this study.

Official Title
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A Randomized Comparison Of Medroxyprogesterone Acetate (MA) And Observation For Prevention Of Endometrial Pathology In Postmenopausal Breast Cancer Patients Treated With Tamoxifen, Phase III

Conditions
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Breast Cancer, Endometrial Cancer

Intervention / Treatment
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* Drug: medroxyprogesterone
* Drug: tamoxifen citrate
* Procedure: adjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following histologically proven diagnoses: Primary invasive adenocarcinoma of the unilateral or bilateral breast Stage I, IIA, or IIB (T1-3, N0-1, M0) No recurrent invasive breast cancer Ductal carcinoma in situ (DCIS) Lobular carcinoma in situ (LCIS) with microinvasion Paget's disease of the nipple No sarcoma, lymphoma, or apocrine, adenocystic, or squamous cell cancer of the breast Currently free of breast cancer (no evidence of disease) No evidence of distant disease on chest x-ray or chest CT scan and mammogram of the opposite breast within the past year Prior definitive local treatment of primary lesion (mastectomy or breast-sparing procedure with radiotherapy) and either axillary node or sentinel node biopsy Surgical margins clear of both infiltrating carcinoma (any type) and DCIS No gross or microscopically positive margins except: Invasive cancer or DCIS at the focal margin treated with definitive radiotherapy Gross or LCIS at the final margin Biopsy requirement waived for DCIS or LCIS with minimal microinvasion Patients with breast-sparing procedure must have received or be planning to receive radiotherapy at start of tamoxifen treatment No endometrial simple or cystic hyperplasia, proliferative changes, complex (adenomatous) or atypical hyperplasia, or carcinoma Patients must be planning one of the following: Starting adjuvant tamoxifen for five years OR Started tamoxifen within 28 days prior to study and planning to receive adjuvant tamoxifen for five years Hormone receptor status: Candidate for adjuvant tamoxifen therapy PATIENT CHARACTERISTICS: Age: Adult Sex: Female Menopausal status: Postmenopausal defined as: At least 1 year since last menstrual period At least 2 months since bilateral oophorectomy prior to breast cancer diagnosis 4-12 months since last menstrual period and FSH elevated to postmenopausal range Postmenopausal estrogen therapy and 55 years of age or older Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Fertile patients must use effective contraception during and for at least 2 months after study No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or stage I or II cancer currently in complete remission No concurrent nonmalignant-related illness that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Adjuvant chemotherapy allowed No concurrent chemotherapy Endocrine therapy: See Disease Characteristics No prior hormonal treatment for breast cancer (except tamoxifen) No concurrent postmenopausal estrogen therapy Radiotherapy: See Disease Characteristics Surgery: See Disease Characteristics No prior or concurrent hysterectomy Other: No prior or current participation in an adjuvant intergroup trial

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tamoxifen alone<br>Tamoxifen alone x 5 years | Drug: tamoxifen citrate<br> <br> Procedure: adjuvant therapy<br> <br> |
| Experimental: Tamoxifen plus MPA<br>Tamoxifen Plus Medroxyprogesterone Acetate (MPA) x 5 years | Drug: medroxyprogesterone<br> <br> Drug: tamoxifen citrate<br> <br> Procedure: adjuvant therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial pathologic diagnosis | Endometrial pathologic diagnosis at 2 years after registration | 2 years after registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial pathologic diagnosis | Endometrial pathologic diagnosis at 5 years after registration | 5 years after registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial cancer, stage I breast cancer, stage II breast cancer, ductal breast carcinoma in situ, lobular breast carcinoma in situ, Paget disease of the breast