Acolbifene in Preventing Cancer in Premenopausal Women at High Risk of Breast Cancer

PRIMARY OBJECTIVES: I. To determine the effect of six months of acolbifene 20 mg/day on Ki-67 in high risk premenopausal women with baseline hyperplasia +/- atypia and Ki-67 positivity of \>= 2%.. SECONDARY OBJECTIVES: I. To determine the effect of six months of acolbifene 20 mg/day on mammographic breast density in high risk premenopausal women. II. To determine the effect of six months of acolbifene 20 mg/day on serum levels of follicular phase bioavailable estradiol, and luteal phase progesterone, testosterone, and fasting IGF-1/IGFBP-3. III. To determine the effect of six months of acolbifene 20 mg/day on epithelial cell cytomorphology and molecular markers such as ER, PgR, and pS2. IV. To determine the effect of six months of acolbifene on markers of cardiovascular risk (C-reactive protein, functional AntiThrombin III, and fasting lipid profile) and bone turnover markers associated with bone mineral density gain or loss (serum osteocalcin and N-telopeptide crosslinks). V. To assess any increase in reported hot flashes, menstrual cycle irregularities, pelvic pain, musculoskeletal complaints, and fatigue from baseline. OUTLINE: Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity. Patients undergo symptom assessment (hot flashes, menstrual abnormalities, pelvic pain, muscle and joint pain, and fatigue) at baseline, 6-8 weeks, monthly for 6 months, and then at 2 weeks after completion of study treatment. Patients undergo random periareolar fine needle aspiration between days 1-10 of menstrual cycle at baseline and at 6 months. Patients also undergo blood sample collection between days 1-10 and days 20-24 of menstrual cycle at baseline and at 6 months. Samples taken between days 1-10 of menstrual cycle are analyzed for Ki-67 expression, cytomorphology, molecular markers (estrogen receptor, progesterone receptor, and pS2 expression), and bioavailable estradiol levels. Samples taken between days 20-24 of menstrual cycle are analyzed for progesterone, testosterone, IGF-1, IGFBP-3, lipid profile, bone-turnover markers (osteocalcin and N-telopeptide crosslinks), C-reactive protein, and functional antithrombin III. After completion of study treatment, patients are followed at 2 weeks.