Afimoxifene in Reducing the Risk of Breast Cancer in Women With Mammographically Dense Breast

Inclusion Criteria

• Women age 40-69 years, or less than 40 years if 5-year breast cancer Gail risk is ≥ 1.66%.
• Mammographically dense breast (heterogeneously dense [C] or extremely dense [D], based on American College of Radiology [ACR] BIRADS fifth edition classification or heterogeneously dense [3] or extremely dense [4], based on ACR BIRADS fourth edition classification) in either breast
• Eastern Cooperative Oncology Group (ECOG) performance status = = 70%)
• White blood cells >= 3,000/microliter
• Absolute neutrophil count >= 1,500/microliter
• Platelets >= 100,000/microliter
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 × institutional upper limit of normal (ULN)
• Creatinine within normal institutional limits
• Participant must have a gynecology examination within the last 3 years, with no atypical hyperplasia and no cancer
• Premenopausal women taking non hormonal intra-uterine device (IUD) birth control method will be eligible, if they have been on the same IUD for at least 3 months prior to enrollment and plan to continue using the same method throughout the study
• Women of child-bearing potential must agree to use a reliable nonhormonal contraceptive method during the study and for 2 months after completing study medications; reliable nonhormonal methods of contraception include barrier contraception and an intra-uterine device (IUD); Note: women who had tubal ligation or had a partner who had undergone a vasectomy (and are monogamous) are eligible for the study and are not required to use barrier contraception
• If the participant is of childbearing potential, she must have a documented negative urine pregnancy test within 7 days prior to randomization
• Willingness to avoid exposing breast skin to natural or artificial sunlight (i.e. tanning beds) for the duration of the study
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 4-OHT gel
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, thromboembolic disease, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant, or had given birth, or nursed at any time during the last 12 months
• Women with a previous history of invasive breast cancer or bilateral ductal carcinoma in situ (DCIS) or current untreated DCIS; women with a history of cancer within the last 3 years, except for non-melanoma skin cancer; women with unilateral DCIS (with or without radiation therapy) are eligible as long as they have an unaffected breast
• Prior bilateral breast surgery (mastectomy, segmental mastectomy, or breast augmentation surgery including breast implants or breast reductions)
• Women with "mosaic mammographic screening views", i.e., whose larger breast size precludes being imaged within a single mammographic screening view
• Women with active liver disease, abnormal uterine bleeding, or prior diagnosis of endometrial hyperplasia
• Prior use of selective estrogen receptor modulators (SERMS) and aromatase inhibitors (AIs) for prevention or therapy
• Skin lesions on the breast that disrupt the stratum corneum (e.g., eczema, ulceration)
• Treatment with any investigational drug or investigational biologic within 30 days of initiating study treatment or during the study