Mammographically Dense Breast Clinical Trial
Official title:
A Randomized, Double-Blind, Placebo-Controlled Study of 4-hydroxytamoxifen Topical Gel in Women With Mammographically Dense Breast
This randomized phase II trial studies how well afimoxifene works in reducing the risk of breast cancer in women with mammographically dense breast. Estrogen can cause the growth of breast cancer cells. Hormone therapy using afimoxifene may fight breast cancer by blocking the use of estrogen by the tumor cells.
PRIMARY OBJECTIVES: I. To estimate and compare the percent change in mammographic breast density (using Cumulus software) from baseline to month 12 in women applying 4mg afimoxifene (4-hydroxytamoxifen [4-OHT]) gel per breast versus placebo. SECONDARY OBJECTIVES: I. To compare the Cumulus versus (vs.) Volpara breast density measurement methods to estimate percent change in mammographic breast density from baseline to month 12 in women applying 4mg of 4-OHT gel per breast vs. placebo. II. To compare the percentage of women who underwent a change in Breast Imaging Reporting and Data System (BIRADS) category, comparing pre-and post- treatment measurements, for recipients of active agent versus placebo. III. To estimate percentage of women with >= 10% absolute decrease in quantitative mammographic density percentage between baseline and 12 months, comparing between treated group 4mg per breast 4-OHT gel to placebo. IV. To describe symptoms assessed by breast cancer prevention trial (BCPT) eight symptom scale (BESS) questionnaire and laboratory toxicity assessment (factor VIII [F VIII], Von Willebrand [vWB] factor, sex hormone-binding globulin [SHBG], lipid profile). V. To evaluate serum measurements of 4-OHT and related metabolite levels and factors related to tamoxifen exposures, such as insulin-like growth factor (IGF) pathway members, C-reactive protein (CRP), estradiol. VI. To evaluate tissue biomarkers (among women undergoing optional pre- and post-treatment biopsies): terminal duct lobular unit (TDLU) involution; collagen structural changes; SETER/PR index: estrogen related transcription, Ki-67, COX-2, p16, CD68. VII. To examine whether any reductions in mammographic density seen after 1 year of 4-OHT vs. placebo gel application persist at 24 months, one year after gel application has stopped. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients apply placebo gel topically to each breast once daily (QD) for up to 52 weeks. ARM B: Patients apply afimoxifene gel topically to each breast QD for up to 52 weeks. After completion of study treatment, patients are followed up at 24 months. ;