Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort.

Non-steroidal anti-inflammatory agents (NSAIDs) are associated with modest inconsistent reductions in breast cancer (BC) risk in population-based cohorts, whereas two focused studies of benign breast disease (BBD) patients have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated BC risk, we assessed whether NSAID use was associated with lower BC risk among BBD patients. Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 BBD patients and 36,751 non-BBD patients, including 3,896 incident BCs over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus BC risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures. BBD patients who reported using NSAIDs experienced lower BC risk (HR=0.87, 95%CI = 0.78-0.97), with similar effects for estrogen receptor (ER)-positive BCs (HR=0.85; 95%CI:0.74-0.97) and ER-negative BCs (HR=0.87; 95%CI:0.59-1.29); among women without BBD, NSAID use was unrelated to risk (HR=1.02, 95%CI = 0.92-1.13; pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar. Among BBD patients, NSAID use appears linked to lower BC risk. Further studies to assess the value of NSAID use among BBD patients are warranted.