Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease

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Abstract
BACKGROUND Biopsy-proven benign breast disease (BBD) is a risk factor for developing breast carcinoma; however, to the authors' knowledge, little is known regarding factors related to progression to carcinoma. A cohort study was conducted to examine the role of cyclooxygenase (COX) polymorphisms and nonsteroidal anti-inflammatory drugs (NSAIDs) in the progression of BBD to breast carcinoma. METHODS Among participants in an ongoing cohort study, 1467 women underwent a breast biopsy for BBD. Of these women, 91 subsequently developed breast carcinoma. Medication data were collected in 1989 and in 1996. COX genotypes were determined using DNA extracted from blood specimens collected in 1989. RESULTS A decrease in breast carcinoma risk was observed among women who reported using aspirin in 1989 (odds ratio [OR] of .46; 95% confidence interval [95% CI], .22–.98) and in 1996 (OR of .47, 95% CI, .18–1.21). Furthermore, a higher frequency, dose, and longer duration of aspirin use were associated with a decrease in the odds of developing breast carcinoma. Overall, no association was observed between COX genotypes and the subsequent development of breast carcinoma. However, among women not using NSAIDs, one COX-2 polymorphism (rs2143416) was found to be significantly associated with the development of breast carcinoma. CONCLUSIONS Findings from the current study suggest that inflammation through COX-2 pathways may play a role in the progression of BBD to breast carcinoma and that aspirin may help to lower the risk of progression to breast carcinoma among women with BBD. Cancer 2006. © 2006 American Cancer Society.