RATIONALE: Chemoprevention therapy uses certain drugs to try to prevent the development or recurrence of cancer. It is not yet known whether bexarotene is effective in preventing breast cancer.

PURPOSE: Randomized clinical trial to study the effectiveness of bexarotene in preventing breast cancer in women who are at genetic risk of developing breast cancer.

Condition	Treatment or Intervention
Breast Cancer	Drug: bexarotene  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer

OBJECTIVES:

• Determine whether bexarotene can modify immunophenotypic markers related to breast cancer progression in women at high genetic risk for breast cancer.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to menopausal status (women with a uterus who have not had a menstrual period for more than 1 year vs any woman over 55 years old vs women 55 years and under without a uterus whose follicle-stimulating hormone is in the postmenopausal range). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral bexarotene once daily on days 1-28.
• Arm II: Patients receive oral placebo as in arm I. In both arms, treatment continues in the absence of unacceptable toxicity or elevation of triglycerides to greater than 800 mg/dL. Patients undergo 2 breast biopsies in the same location on days 1 and 29.

Patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study within 4 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Known carrier of a BRCA-1 or BRCA-2 mutation
• Copy of laboratory report stating results must be available for review OR
• At risk for carrying a BRCA-1 or BRCA-2 mutation
• At least 10% risk by Parmigiana probability model
• Must have at least 1 breast that has never been involved with cancer and has not been irradiated
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 4,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hematocrit greater than 30%

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• ALT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN
• Albumin no greater than 1.5 times ULN
• No biliary tract disease

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and for 1 month after study therapy
• Triglycerides normal
• Thyroid-stimulating hormone and thyroxine normal
• Willing to undergo 2 duplicate needle biopsies of the breast
• Willing to undergo genetic testing for BRCA-1 and BRCA-2
• No uncontrolled hyperlipidemia
• No nontoxic goiter or thyroid enlargement
• No severe underlying chronic illness or disease
• No uncontrolled diabetes
• No history of pancreatitis
• No cancer within the past year except skin cancer or carcinoma in situ of the cervix (defined from the date of first diagnosis)
• No concurrent alcohol use (greater than 3 drinks or its equivalent per day)

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 1 year since prior chemotherapy for a neoplasm

Endocrine therapy

• More than 3 months since prior postmenopausal hormonal therapy (including estrogens or progestins)
• More than 3 months since prior tamoxifen or other selective estrogen-receptor modulators
• No concurrent hormone replacement therapy
• Concurrent thyroid hormone supplementation allowed

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified

Other

• More than 30 days since prior investigational medications
• More than 3 months since prior oral vitamin A supplements greater than the recommended daily requirement (5,000 IU) or therapeutic oral or topical vitamin A derivatives (e.g., isotretinoin)
• No concurrent participation in a study of an investigational agent
• No concurrent medications known to be associated with pancreatic toxicity or to increase triglyceride levels

District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Cancer Therapy and Research Center, San Antonio,  Texas,  78229,  United States; Recruiting
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Richard M. Elledge, MD,  Study Chair,  Baylor College of Medicine   

Study ID Numbers:  CDR0000271913; BCM-H-9315
Record last reviewed:  August 2004
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055991
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05