bexarotene in preventing breast cancer in women at genetic risk

Conditions: Breast Cancer

Summary: 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.

Eligibility 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

Keywords: breast cancer