S9630, Medroxyprogesterone in Treating Women With Breast Cancer
S9630, Medroxyprogesterone in Treating Women With Breast Cancer
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.
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.
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