Breast Cancer
Conditions
Keywords
breast cancer
Brief 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.
Detailed description
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.
Interventions
DRUGbexarotene
This drug is a retinoid. The anti-tumor action of retinoids, as well as their potential in chemoprevention, supports the need to further identify the spectrum of responsive tumors, to identify the molecular mechanisms associated with retinoid action, and to identify and develop new retinoids that have unique properties and an improved therapeutic index.
Sponsors
National Cancer Institute (NCI)
Baylor Breast Care Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Chemopreventive effect as determine by a modification of the immunophenotypic characteristics of normal breast tissue at day 29 during study treatment and day 30 after study completion | — |
Secondary
| Measure | Time frame |
|---|---|
| Apoptosis at day 29 during study treatment | — |
Countries
United States
Outcome results
None listed