Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer

Description

PRIMARY OBJECTIVE:

I. To determine if there is a difference in change in expression of the endocrine resistance gene anterior gradient 2 (AGR2) in benign breast tissue of premenopausal women at increased risk for breast cancer randomized to acolbifene 20 mg versus (vs) tamoxifen 5 mg orally daily for 6 months.

SECONDARY OBJECTIVES:

I. To determine if there is significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg as assessed on the Estrogen Response Gene Index (ERGI) in benign breast tissue.

II. To determine if there is significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg on mammographic density as measured by change in fibroglandular volume (FGV) and mammographic percent dense volume.

III. To determine if there is a significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg on Menopause-Specific Quality of Life Questionnaire (MENQOL) or Hot Flash Score.

EXPLORATORY OBJECTIVES:

I. Assess within arm change in breast epithelial cell protein expression of Ki-67 in specimens with >= 2% baseline Ki-67.

II. Assess within arm change in bioavailable serum estradiol, testosterone, progesterone.

III. Association of baseline anti-Mullerian hormone (AMH) (>= 1 ng/ml associated with normal ovarian reserve) with 6-month serum estradiol and change in tissue estrogen responsive gene expression (ERGI and AGR2).

IV. Association of tamoxifen and acolbifene parent drug and active metabolite levels with change in tissue estrogen response genes and mammographic density.

V. Assess within arm change of AGR2, Forkhead box protein A1 (FOXA1), estrogen receptor (ER), progesterone receptor (PR) proteins on residual fixed specimens acquired by random periareolar fine needle aspiration (RPFNA) and processed to blocks.

VI. Assess within arm change in metabolic measures including triglycerides, measures of insulin sensitivity and thyroid binding globulin (Kansas University Medical Center [KUMC] participants only).

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive acolbifene orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo three-dimensional (3D) mammography and collection of blood samples during screening and at the end of acolbifene treatment. In addition, patients undergo RPFNA during screening and on day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

GROUP II: Patients receive tamoxifen PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D mammography and collection of blood samples during screening and at the end of tamoxifen treatment. In addition, patients undergo RPFNA during screening and day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

After completion of study treatment, patients are followed up between 21-35 days.