Regular use of aspirin and other non-steroidal anti-inflammatory drugs and breast cancer risk for women at familial or genetic risk: a cohort study

Abstract

Background 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. 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. Methods We 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). Results From 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. Conclusion Regular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk. Electronic supplementary material The online version of this article (10.1186/s13058-019-1135-y) contains supplementary material, which is available to authorized users.

Aspirin might reduce the incidence of breast cancer

“…[ 16 , 17 , 35 – 43 ] As only a few studies reported subgroup results, we used data in duplicate studies if studies with the largest number of cancer cases didn’t report those to allow studies to be as inclusive as possible. [ 16 , 35 , 37 , 38 , 42 ] At last, 38 studies met the predetermined criteria for inclusion, with 22 cohort studies [ 3 , 4 , 6 , 10 – 15 , 44 – 56 ] and 16 case–control studies. [ 5 , 8 , 57 – 70 ] Among the 1,926,742 participants of this meta-analysis, there were 97,099 incident breast cancers.…”

“…Numerous epidemiologic studies have investigated the relationships between use of aspirin and risk of breast cancer. Some studies have suggested a modest reduction in breast cancer risk in relation to use of aspirin, [ 3 – 5 ] but a randomized clinical trial of long term use of aspirin and some of recent studies did not support a protective role. [ 6 – 8 ]…”

“…Besides, 6 relevant studies were published recently. [ 3 , 4 , 6 – 8 ] So far, the effect of aspirin on the occurrence of breast cancer has remained uncertain.…”

Translate but validate: necessary steps in improving the use and utility of cancer risk models

“…To date, there has not been strong evidence of GXE, at least for the established breast cancer risk factors that have been tested in large consortia studies [7]. However, most risk models still do not include other risk factors like physical activity and aspirin which are consistent risk factors across the spectrum of absolute risk [8,9].…”

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“…The estimate of new cancer cases reached 18.1 million worldwide in 2018 [1], with a constantly growing trend that needs to be contrasted by efficacious (chemo) preventive strategies able to counteract the dreadful global burden of this disease [2]. Several preclinical, epidemiological and clinical studies proposed nonsteroidal anti-inflammatory drugs (NSAIDs) as one of the most promising class of compounds for the prevention of different cancer types, including mammary tumors [3], even if their use in long-term treatment is limited by side effects due to cyclooxygenase (COX) inhibition.…”