Breast Cancer, Endometrial Cancer
Conditions
Keywords
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
Brief summary
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
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.
Interventions
Sponsors
National Cancer Institute (NCI)
Cancer and Leukemia Group B
SWOG Cancer Research Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endometrial pathologic diagnosis | 2 years after registration | Endometrial pathologic diagnosis at 2 years after registration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endometrial pathologic diagnosis | 5 years after registration | Endometrial pathologic diagnosis at 5 years after registration |
Countries
United States
Outcome results
None listed