Prospective Study of Regular Aspirin Use and the Risk of Breast Cancer

Background: Evidence suggests that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can inhibit tumor development in the large bowel. An inverse association between the use of NSAIDs and the incidence of breast cancer has been observed, but this association has not been statistically significant in all studies. Purpose: We analyzed data from the prospective Nurses' Health Study to evaluate the influence of aspirin use on breast cancer risk. Methods: We studied a population of 89 528 female registered nurses who reported no history of breast or other cancers (excluding nonmelanoma skin cancer) and who returned a mailed questionnaire in 1980 that elicited information concerning breast cancer risk factors and current and past aspirin use. Follow-up questionnaires were mailed to the participants every 2 years; the women were followed through 1992. Information concerning current aspirin use was obtained from each biennial questionnaire, except in 1986. Cases of breast cancer were identified through questionnaire responses, and permission was sought for a review of medical records to confirm the diagnoses. Our analysis was based on 2414 cases of invasive breast cancer, which included 2303 cases confirmed with medical records and 111 cases for which no records were obtained. Relative risks (RRs) with 95% confidence intervals (CIs), adjusted for age or age plus other known or potential breast cancer risk factors (i.e., multivariate), were calculated. Results: Regular aspirin use (two or more tablets per week) in 1980 was unrelated to breast cancer incidence during the succeeding 12-year period (with no regular aspirin use as the referent, multivariate RR = 1.03; 95% CI = 0.95-1.12). The corresponding risk estimate for consistent regular aspirin use during the period from 1980 through 1988 was 1.01 (95% CI = 0.80-1.27). The risks were similar for heavy aspirin use (for more than two tablets per day [i.e., >14 per week] in 1980 and in 1980 through 1988, the multivariate RRs [95% CIs] were 1.05 [0.89-1.23] and 1.09 [0.75-1.60], respectively) and for extended durations of regular use (e.g., for 20 years or more of regular use, multivariate RR = 1.00; 95% CI = 0.71-1.41). Conclusion: Our results indicate that regular aspirin use does not reduce the risk of breast cancer. [J Natl Cancer Inst 1996;88:98893] Mounting evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, can inhibit the development of tumors in the large bowel. In animal models of colon carcinogenesis, certain NSAIDs reduced the incidence of tumors in general, as well as the number of tumors per animal {1-4). In human trials (5,6) and in a series of case reports (710), specific NSAIDs were shown to induce the regression of existing adenomatous polyps of the colon and to prevent recurrences in persons genetically at risk. Epidemiologic studies suggest that NSAIDs may also be effective in the prevention of colorectal cancer (11-19). Inverse associations between the use of NSAIDs and the occurrence of sporadic colonic adenomas (17,19-21) suggest that NSAIDs may inhibit an early event in colon carcinogenesis. The therapeutic effects of NSAIDs are related to their ability to block the enzyme cyclooxygenase and, in tum, to inhibit prostaglandin biosynthesis. Prostaglandins may serve as cofactors in carcinogenesis (22), with postulated effects ranging from direct mutagenesis (one byproduct of arachidonic acid metabolism is malondialdehy de, a direct-acting mutagen) to tumor promotion, immune suppression, and facilitation of metastasis. However, other evidence suggests that the cancer inhibitory effects of NSAIDs may be independent of their effects on prostaglandin synthesis (23).