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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

Phase 3
18 Years
Not Enrolling
Breast Cancer, Endometrial Cancer

Thank you

Trial Information

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


- 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.

Inclusion Criteria


- 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

- 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



- Adult


- 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


- Not specified


- Not specified


- Not specified


- 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


Biologic therapy:

- Not specified


- 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


- See Disease Characteristics


- See Disease Characteristics

- No prior or concurrent hysterectomy


- No prior or current participation in an adjuvant intergroup trial

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Endometrial pathologic diagnosis

Outcome Description:

Endometrial pathologic diagnosis at 2 years after registration

Outcome Time Frame:

2 years after registration

Safety Issue:


Principal Investigator

Ronald K. Potkul, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Loyola University


United States: Food and Drug Administration

Study ID:




Start Date:

March 1997

Completion Date:

December 2009

Related Keywords:

  • Breast Cancer
  • Endometrial Cancer
  • 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
  • Breast Neoplasms
  • Endometrial Neoplasms
  • Adenoma



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