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Mary Beth Terry, PhD; Marilie D. Gammon, PhD; Fang Fang Zhang, MD, MPH; Heba Tawfik, MD, MPH; Susan L. Teitelbaum, PhD; Julie A. Britton, PhD; Kotha Subbaramaiah, PhD; Andrew J. Dannenberg, MD; Alfred I. Neugut, MD, PhD

JAMA. 2004;291:2433-2440.

Context  Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with a decrease in the risk of several cancers, including breast cancer. NSAIDs inhibit cyclooxygenase activity and thereby reduce prostaglandin synthesis; prostaglandins stimulate aromatase gene expression and thereby stimulate estrogen biosynthesis. Given the importance of estrogen in the pathogenesis of breast cancer, the ability of aspirin and other NSAIDs to protect against breast cancer could vary according to hormone receptor status.

Objectives  To determine the association between the frequency and duration of use of aspirin and other NSAIDs and breast cancer risk and to investigate whether any observed association is more pronounced for women with hormone receptor–positive breast cancers.

Design, Setting, and Patients  Population-based case-control study of women with breast cancer, including in-person interviews conducted on Long Island, NY, during 1996-1997 (1442 cases and 1420 controls).

Main Outcome Measure  Incident invasive and in situ breast cancer by aspirin and NSAID use and hormone receptor status.

Results  Ever use of aspirin or other NSAIDs at least once per week for 6 months or longer was reported in 301 cases (20.9%) and 345 controls (24.3%) (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.66-0.97 for ever vs nonusers). The inverse association was most pronounced among frequent users (7 tablets per week) (OR, 0.72; 95% CI, 0.58-0.90). The results for ibuprofen, which was used by fewer women on a regular basis, were generally weaker (OR, 0.78; 95% CI, 0.55-1.10 for <3 times per week vs OR, 0.92; 95% CI, 0.70-1.22 for 3 times per week). Use of acetaminophen, an analgesic that does not inhibit prostaglandin synthesis, was not associated with a reduction in the incidence of breast cancer. The reduction in risk with aspirin use was seen among those with hormone receptor–positive tumors (OR, 0.74; 95% CI, 0.60-0.93) but not for women with hormone receptor–negative tumors (OR, 0.97; 95% CI, 0.67-1.40).

Conclusion  These data add to the growing evidence that supports the regular use of aspirin and other NSAIDs (which may operate through inhibition of estrogen biosynthesis) as effective chemopreventive agents for breast cancer.

Author Affiliations: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY (Drs Terry, Zhang, Tawfik, and Neugut); Herbert Irving Comprehensive Cancer Center (Drs Terry and Neugut) and Department of Medicine (Dr Neugut), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Epidemiology, University of North Carolina, School of Public Health, Chapel Hill (Dr Gammon); Department of Community Medicine, Mt Sinai School of Medicine, New York, NY (Drs Teitelbaum and Britton); and Department of Medicine, Weill Medical College of Cornell University and Strang Cancer Prevention Center, New York, NY (Drs Subbaramaiah and Dannenberg).

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