Abstract
BACKGROUND: Studies investigating the associations of self-reported aspirin use and mammographic breast density (MBD) have reported conflicting results. Therefore, we investigated the associations of aspirin metabolites with MBD in premenopausal women. METHODS: We performed this study on 705 premenopausal women who had a fasting blood draw for metabolomic profiling. We performed covariate-adjusted linear regression models to calculate the least square means of volumetric measures of MBD [volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV)] by quartiles of aspirin metabolites [salicyluric glucuronide, 2-hydroxyhippurate (salicylurate), salicylate, and 2,6-dihydroxybenzoic acid]. RESULTS: Approximately 13% of participants reported taking aspirin in the past 12 months. Aspirin users had higher levels of 2-hydroxyhippurate (salicylurate), salicylate, and salicyluric glucuronide (peak area) than nonusers, but only the mean peak area of salicyluric glucuronide was increased by both dose (1-2 tablets per day = 1,140,663.7 and ≥3 tablets per day = 1,380,476.0) and frequency (days per week: 1 day = 888,129.3, 2-3 days = 1,199,897.9, and ≥4 days = 1,654,637.0). Aspirin metabolites were not monotonically associated with VPD, DV, or NDV. CONCLUSIONS: Given the null results, additional research investigating the associations of aspirin metabolites in breast tissue and MBD is necessary. Impact: Elucidating the determinants of MBD, a strong risk factor for breast cancer, can play an important role in breast cancer prevention. Future studies should determine the associations of nonaspirin NSAID metabolites with MBD.