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.

Condition	Treatment or Intervention	Phase
Endometrial Cancer stage I breast cancer stage II breast cancer intraductal breast carcinoma lobular breast carcinoma in situ Paget's disease of the breast	Drug: medroxyprogesterone  Drug: tamoxifen  Procedure: adjuvant therapy  Procedure: antiestrogen therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: progestin therapy	Phase III

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States
Alaska
      Providence Alaska Medical Center, Anchorage,  Alaska,  99519-6604,  United States
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States
      Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda,  California,  92357,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Hines, Hines,  Illinois,  60141,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States
      Providence Cancer Institute at Providence Hospital - Southfield, Southfield,  Michigan,  48075,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0948,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States
New Jersey
      Cooper University Hospital, Camden,  New Jersey,  08103,  United States
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Mount Sinai Medical Center, New York,  New York,  10029,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lenoir Memorial Hospital Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
Ohio
      Arthur G. James Cancer Hospital at Ohio State University, Columbus,  Ohio,  43210-1240,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States
Tennessee
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Ronald Keith Potkul, MD,  Study Chair,  Loyola University   
Barbara L. Smith, MD, PhD,  Study Chair,  Massachusetts General Hospital   

Study ID Numbers:  CDR0000065314; SWOG-S9630; CALGB-49901; SWOG-9630; NCT00002920
Record last reviewed:  January 2005
Last Updated:  January 10, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002920
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08