Non-steroidal anti-inflammatory drug use and breast cancer risk in a prospective cohort study

Abstract

Introduction In past decades, evidence from both experimental and observational studies has accumulated suggesting that chronic inflammation could promote breast cancer development. Therefore, nonsteroidal anti-inflammatory drugs (NSAIDs), a class of drugs commonly used to treat pain, fever and inflammation, has been proposed as potential chemo-preventive agents for breast cancer. Although inverse associations between NSAIDs and breast cancer risk have been reported in most case-control studies, results from cohort studies are less consistent. Our objective was to assess the association between NSAID use and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Self-reported information on NSAID use at baseline has been collected in five EPIC countries (France, Denmark, United Kingdom, the Netherlands and Germany). Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with breast cancer incidence with adjustment for potential confounders. We also assessed effect modification by breast cancer risk factors and examined the associations within specific breast cancer subtypes. Results Among the 140,981 women included in the analysis, 7% were regularly using NSAIDs at baseline. During a median follow-up time period of 13 years, 7379 incident breast cancer cases were diagnosed (816 in situ and 6563 invasive). In multivariable models, there was no statistically significant association between regular NSAID use and breast cancer risk overall. Compared with women who were not regular users at baseline, the HR for regular users of NSAIDs was 0.99 (95% CI = 0.90 to 1.08). Risk estimates did not vary significantly by histological subtypes, by hormone receptor status of the tumor, by breast cancer risk factors or by country (all Pinteraction/heterogeneity between 0.10 and 0.92). However, among postmenopausal women, a statistically significant interaction was observed between NSAID use and ever use of menopausal hormonal therapy (MHT) for invasive breast cancer cases [among MHT ever users: HRNSAID use = 0.84 (0.73–0.96); among MHT never users: HRNSAID use = 1.08 (0.93–1.25); Pinteraction = 0.05], but not for in situ cases [among MHT ever users: HR NSAID use = 1.25 (0.82–1.92); among MHT never users: HR NSAID use = 1.18 (0.81–1.73); Pinteraction = 0.99]. Conclusions and perspectives Our results indicate potential effect modification of MHT use on the association between use of NSAIDs and breast cancer risk which deserves in-depth investigation in studies with accurate data on both NSAID and MHT use, including type, dosage, frequency and duration of use. We are currently exploring this further in a study within the French-EPIC cohort (E3 N cohort) including 61,107 women with individual drug-reimbursement data available from years 2004 to 2011, including dose, duration and subtypes of NSAIDs. If the interaction between MHT use, NSAIDs and breast cancer risk is confirmed, this could have public health implications with respect to how MHT is administered.