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Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women.

ABSTRACT: BACKGROUND:Although anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent. METHODS:We investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on lifestyle and medical history has been collected biennially by questionnaires and matched with data from a drug reimbursement database covering the period 2004-2014. Women who self-reported current NSAID use in the 2000 or 2002 questionnaires or with at least two reimbursements in any previous 3-month period were defined as exposed to NSAIDs. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for the association of NSAID use with BC risk. RESULTS:In the current analysis, 62,512 postmenopausal women were followed between 2004 and 2014 (9?years on average, starting at a mean age of 63?years; 2864 incident BC). In multivariable models, there was no statistically significant association between NSAID use and BC risk [HR?=?1.00 (0.92-1.08), compared with non-exposed women]. The NSAID-BC associations did not differ by NSAID types, BC subtypes, risk factors, and comorbidities, nor by duration and dose of use. However, a statistically significant interaction was observed by proton pump inhibitor (PPI) drug use (Pinteraction?=?0.01) whereby a decreased risk of BC with NSAID use was only observed among women who also used PPI before. CONCLUSION:Only women who used NSAIDs after having used PPI had a lower risk of BC. This result is novel and requires replication in other studies.

SUBMITTER: Cairat M

PROVIDER: S-EPMC7603705 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women.

Cairat Manon M Al Rahmoun Marie M Gunter Marc J MJ Severi Gianluca G Dossus Laure L Fournier Agnès A

Breast cancer research : BCR 20201031 1

<h4>Background</h4>Although anti-inflammatory agents could theoretically have anticancer properties, results from cohort studies on nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer (BC) risk are inconsistent.<h4>Methods</h4>We investigated the association between NSAID use and BC incidence in the French E3N prospective cohort, which includes 98,995 women born between 1925 and 1950 and insured by a health insurance plan that covers mostly teachers. Self-reported information on life ...[more]

PMID: 33129324

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Project description:Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition.Postmenopausal women enrolled in the Women's Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06-1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01-1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10-1.24; P<0.001 and naproxen only: HR, 1.22; 1.12-1.34; P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR, 1.01; 0.95-1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93-1.07; P=0.996).Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk.www.clinicaltrials.gov. Unique identifier: NCT00000611.

Dataset Information

Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women.

Publications

Use of nonsteroidal anti-inflammatory drugs and breast cancer risk in a prospective cohort of postmenopausal women.

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