Effect of Aspirin on Mammogram Density in Healthy Postmenopausal Women With a Moderate or High Level of Breast Density

OBJECTIVES: Primary * Compare the effect of acetylsalicylic acid (aspirin) vs placebo on mammographic density in healthy postmenopausal women with a moderate or high level of breast density. Secondary * Determine whether there is a differential response in mammogram density to aspirin treatments in individual homozygous wild-type, heterozygous, and homozygous variant for several UGT gene polymorphisms. * Determine the effect of aspirin therapy on potential adverse events, including gastrointestinal symptoms and signs, bleeding events, blood pressure, and other major comorbidities and hospitalizations, as well as generalized symptoms, in these participants. * Determine the effects of aspirin therapy on putative biomarkers of breast and ovarian cancer that are currently being validated as part of ongoing Fred Hutchinson Cancer Research Center Ovarian SPORE activities. * Determine the effects of aspirin therapy on levels of serum estradiol, estrone and sex hormone binding globulin (SHBG) as measured by radioimmunoassay at baseline and 6 month timepoints OUTLINE: This is a randomized, placebo-controlled, double-blind study. Participants are randomized to 1 of 2 treatment arms. * Arm I: Participants receive oral acetylsalicylic acid (aspirin) daily for 6 months. * Arm II: Participants receive oral placebo daily for 6 months. In both arms, participants undergo a repeat mammogram at 6 months. Blood and urine samples are collected at baseline and at 6 months. Single-nucleotide polymorphisms in the UGT genes and variable number of tandem repeat-type polymorphisms are genotyped. PROJECTED ACCRUAL: A total of 144 participants will be accrued for this study.