Modulation of Breast Cancer Risk by Nonsteroidal Anti-inflammatory Drugs

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) clearly reduce the risk of human colorectal neoplasia in epidemiological and prospective randomized clinical studies of aspirin and nonaspirin NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs ( 1 – 3 ). In contrast, the epidemiological and clinical data on NSAIDs in reducing breast cancer risk are not consistent. This inconsistency is likely attributable to contrasting expression patterns of COX-2, a key target of NSAIDs, in breast and colon neoplasia ( 4 , 5 ), and to differing activities of individual NSAIDs (which have varying selectivity for COX-2 vs COX-1), including a potentially selective impact of certain NSAIDs on hormone receptor – positive breast tumors. In this issue of the Journal, Takkouche et al. ( 6 ) report an extensive meta-analysis (involving 38 studies) supporting an inverse association between NSAID use and risk of breast cancer . They found a statistically signifi cant reduction in breast cancer risk associated with use of any NSAID (relative risk [RR] = 0.88, 95% confi dence interval [CI] = 0.84 to 0.93) and similar associations for aspirin (RR = 0.87, 95% CI = 0.82 to 0.92) and ibuprofen (RR = 0.79, 95% CI = 0.64 to 0.97). They found no evidence of a dose – response relationship, and some studies indicated that coxibs were also associated with a lower risk of breast cancer ( 7 , 8 ). This large-scale meta-analysis is consistent with several smaller meta-analyses ( 9 – 12 ). Furthermore, NSAIDs can prevent experimental breast cancer in numerous rodent models ( 4 , 5 ). Why then do individual observational and clinical studies vary substantially in