Conditions: Breast Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 25
Healthy volunteers: yes

Brief summary:
This phase II trial is studying how well acolbifene works in preventing cancer in premenopausal women at high risk of breast cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acolbifene may stop cancer from growing or coming back.

Detailed description:
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.

Arms:
arm 1: Patients receive oral acolbifene hydrochloride once daily for 6 months in the absence of unacceptable toxicity.

Interventions: intervention 1: acolbifene hydrochloride
Intervention descriptions: intervention 1: Given orally

Protocol document: