Abstract
BackgroundThe use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers.MethodsWe analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history. The prospective cohort was further restricted to women without breast cancer when medication history was asked by questionnaire. Women were recruited from seven study centers in the United States, Canada, and Australia. Associations were estimated using multivariable Cox proportional hazards regression models adjusted for demographics, lifestyle factors, family history, and other medication use. Women were classified as regular or non-regular users of aspirin, COX-2 inhibitors, ibuprofen and other NSAIDs, and acetaminophen (control) based on self-report at follow-up of ever using the medication for at least twice a week for ≥1 month prior to breast cancer diagnosis. The main outcome was incident invasive breast cancer, based on self- or relative-report (81% confirmed pathologically).ResultsFrom fully adjusted analyses, regular aspirin use was associated with a 39% and 37% reduced risk of breast cancer in the prospective (HR = 0.61; 95% CI = 0.33–1.14) and combined cohorts (HR = 0.63; 95% CI = 0.57–0.71), respectively. Regular use of COX-2 inhibitors was associated with a 61% and 71% reduced risk of breast cancer (prospective HR = 0.39; 95% CI = 0.15–0.97; combined HR = 0.29; 95% CI = 0.23–0.38). Other NSAIDs and acetaminophen were not associated with breast cancer risk in either cohort. Associations were not modified by familial risk, and consistent patterns were found by BRCA1 and BRCA2 carrier status, estrogen receptor status, and attained age.ConclusionRegular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk.
Highlights
The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk
Regular aspirin users had a higher 1-year BOADICEA risk score than non-regular users, which is influenced by baseline age; a smaller proportion of aspirin users had a known mutation in the BRCA1 or BRCA2 gene
In summary, our findings add to growing evidence for an association between regular use of aspirin and COX-2 inhibitors and reduced breast cancer (BC) risk
Summary
The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. Women vary greatly in their underlying familial risk of breast cancer (BC). Those with an affected first-degree relative are on average at 2-fold increased risk of BC. The two leading risk-reduction strategies for women at increased BC risk are risk-reducing mastectomy, which could reduce risk by over 90% [3], and use of medications such as the selective estrogen receptor modulators or aromatase inhibitors, which reduce risk of estrogen receptor (ER)-positive BC by about 30–65% [4,5,6]. Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors could be one such alternative. Even if regular NSAID use proves to be an effective BC prevention strategy, as with other risk-reducing options, the potential benefits of NSAIDs will need to be weighed against the potential harms of long-term use [16,17,18,19,20,21]
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