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Abstract & Commentary
Synopsis: Regular use of aspirin and other nonsteroidal anti-inflammatory agents (NSAIDs) may reduce the risk of breast cancer.
Source: Terry MB, at al. JAMA. 2004;291:2433-2440.
Terry and colleagues hypothesized that aspirin and other non-steroidal anti-inflammatory agents (NSAIDs) protect against breast cancer by inhibiting production of estrogen and or progesterone; thus, the reduction in breast cancer risk associated with NSAID use would be greater for estrogen and progesterone receptor positive breast cancers. To address these issues, they undertook a population-based, case-control study of English-speaking New York women with breast cancer. This cohort has been previously described.1 In brief, it consists of mostly white women between the ages of 20 and 80 who are well characterized, including information about many lifestyle factors and all known risk factors for breast cancer. The current report includes 1141 cases and 1075 aged-matched controls. NSAID use was determined both by a questionnaire and by a structured interview that focused on the 12 months prior to diagnosis of breast cancer. "Regular use" of NSAIDs was defined as use at least 4 times per week for at least 3 months, initiated at least a year prior to diagnosis. "Ever use" was defined as at least once per week for 6 months or longer. There was no attempt to estimate dose. Participants were asked about aspirin, ibuprofen, and acetaminophen (acetaminophen was a control variable). In their analysis, Terry et al controlled for many variables (including things that I didn’t even know had any relationship to the risk of breast cancer).
In this study, 20.9% of breast cancer patients and 24.3% of controls reported "ever use" of aspirin, (defined as at least once per week for 6 months or longer). This was a statistically significant difference (OR, 0.8; CI, 0.66-0.97), but when broken down by in situ vs invasive cancers, was statistically significant only for the invasive cancers. The protective effect of aspirin was significant both for premenopausal and for postmenopausal women. Fewer women reported ever use of ibuprofen or of acetaminophen, and neither of these was associated with a reduced risk of breast cancer. There did appear to be a "dose-dependent" relationship between frequency of aspirin use and reduced risk of breast cancer, with greater reduction in risk for more frequent use (but not for longer use). The reduction in risk was greater for "regular use" (as opposed to "ever use," OR, 0.74; CI, 0.59-0.92). The protective effect of aspirin against breast cancer was statistically significant for every receptor category except both estrogen and progesterone negative tumors, and this was most pronounced among post-menopausal women.
Comment by Barbara A. Phillips, MD, MSPH
Although this paper and the accompanying editorial2 briefly review a fairly large body of literature that demonstrates reduction in breast cancer with NSAID use, I must confess that this is news to me. And it may well be news to your patients; this article received a lot of attention in the lay press. What is new about this paper is the demonstration that the protective effect of aspirin is strongest against hormone receptor positive tumors. The putative basis for this effect is blocking cyclooxygenase (COX), which catalyze the synthesis of prostaglandins, which increase the production of both estrogen and progesterone, which are known to promote the development of breast cancer.
So now, in addition to reducing the risk of cardiovascular disease3 and colorectal cancer,4 aspirin use may also reduce the risk of hormone receptor positive breast cancer (the most common cancer in nonsmoking women). And it doesn’t take very much, since there was a reduction with use 4 times a week for 3 or more months, or even with once a week for 6 months of longer. As is often the case with important work, this article raises many questions. Would there be an even greater reduction in risk with more intense aspirin use? Does timing of use within a woman’s lifespan matter? What is the optimum dosage?
While awaiting answers to these and other questions, it is not unreasonable to encourage regular use of this amazing drug (aspirin) in nonsensitive patients. I am taking it myself!
Dr. Phillips, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington, KY, is Associate Editor of Internal Medicine Alert.
1. Gammon MD, et al. Breast Cancer Res Treat. 2002;74: 235-254.
2. DuBois RN. JAMA. 2004;291:2488-2489.
3. Mueller RD, Scheidt S. Circulation. 1994;89:432-449.
4. Smalley W, Dubois RN. Adv Pharmacology. 1997;39: 1-20.