Abstract
Abstract Background Statin drugs lower cholesterol and prevent cardiovascular disease. Laboratory and epidemiologic evidence suggests that statins may also have anti-cancer properties. Published associations between statin use and breast cancer incidence are heterogeneous. Few studies have comprehensively addressed confounding by lifestyle and reproductive factors, or detection bias due to potentially higher screening rates among medication users. The most recent study on this topic reported an increased risk of invasive breast cancer among statin users. Methods To improve upon the present evidence base we studied the association between statin use and incident breast cancer among 79,518 postmenopausal women in the Nurses' Health Study cohort. We followed these women from 2000 (the year statin exposure was first ascertained prospectively) until the first of breast cancer diagnosis, death from any cause, or the end of follow-up in 2012. We defined statin exposure as current or former use (both factored with duration) or never use. We fit Cox regression models to estimate associations, encoding statin use and covariates as time-dependent variables updated every two years. We evaluated confounding by adiposity, reproductive history, menopausal hormone therapy, family history of breast cancer, history of benign breast disease and diabetes, alcohol consumption, physical activity, and use of co-medications. We also measured associations among those cohort members who underwent screening mammograms every two years. Results Over 823,086 person-years of follow-up, 3,055 cases of invasive breast cancer were diagnosed (1,078 of which were among statin users). Compared with non-users, statin users were somewhat older, had a higher mean BMI, were more likely to be users of aspirin, beta blockers, calcium channel blockers, digoxin, and ACE inhibitors, had a higher prevalence of diabetes, and were more likely to undergo mammographic screening. Current users of any statin had a similar rate of breast cancer incidence as never users (for current users of ≥8 years' duration, HRadj=1.1, 95% CI: 0.91, 1.3). Analyses of specific statin exposures among new initiators of therapy in 2004 returned similarly null associations (for current use of hydrophilic statins, HRadj=1.0, 95% CI: 0.82, 1.3; for current use of lipophilic statins, HRadj=1.1, 95% CI: 0.95, 1.3). Associations did not vary substantially by duration of statin use or according to breast cancer subtypes defined by histology (invasive ductal vs. invasive lobular disease) or estrogen receptor status. Statin use was not associated with incident breast carcinoma in situ. These results were similar in analyses restricted to women who underwent regular screening mammograms. Conclusions Our results indicate that cholesterol-lowering statin therapy neither increases nor decreases breast cancer incidence rate in postmenopausal women. Considering the latest report indicated an increased breast cancer risk among statin users, our neutral findings should reassure physicians that statin therapy for the prevention of cardiovascular disease is safe with respect to breast cancer risk. Citation Format: Ahern TP, Tamimi RM, Chen WY, Garber JE, Eliassen AH, Borgquist S. Statin use and breast cancer incidence in the Nurses' health study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD1-02.
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