Bexarotene in Preventing Breast Cancer in Women at Genetic Risk
Bexarotene in Preventing Breast Cancer in Women at Genetic Risk
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.
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.
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