Abstract 5492: Use of beta blockers, ACE inhibitors, and angiotensin receptor blockers and risk of breast cancer recurrence: A Danish nationwide cohort study

Abstract

Abstract Background: Some studies indicate an anti-cancer effect of certain antihypertensive medications. Beta blockers (BB) inhibit binding of catecholamines to their receptors. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) interrupt the renin-angiotensin system. Both adrenergic and angiotensin activity have been implicated in malignant progression. We conducted a Danish nationwide prospective cohort study to estimate associations between use of these medications and the recurrence rate among breast cancer survivors. Methods: We enrolled Danish women diagnosed with stage I-III invasive breast cancer between 1996-2003 who were reported to the Danish Breast Cancer Cooperative Group (DBCG). Data on patient and tumor characteristics, primary and adjuvant therapy, and recurrence follow-up were ascertained from the DBCG registry. We linked this cohort to the National Registry of Medicinal Products, from which we ascertained pre- and post-diagnosis prescriptions for BB, ACEi, ARBs, and potentially confounding co-medications. Exposure status was updated yearly, with exposure in a given interval defined as having filled at least one prescription for the drug of interest during that interval. Exposures to BB, ACEi, and ARBs were classified as 1) use of any drug in the class, and 2) by purity of the prescription (that is, whether or not tablets were combinations with diuretics or calcium channel blockers). We also evaluated exposure to specific BB with high prevalence. In analyses based on purity and on specific drugs, subjects who switched between exposure types over follow-up were excluded. Recurrence associations were estimated with Cox regression models, in which drug exposures were coded as time-varying covariates lagged by 1 year. Associations were adjusted for prognostic factors, comorbidity, and potentially confounding co-medications. Results: We enrolled 18,733 breast cancer survivors who experienced 3,414 recurrences over 111,010 person-years. There were 3,660 BB users, 3,075 ACEi users, and 1,989 ARB users; median durations of use of these drugs were 4.7, 4.0, and 5.0 years, respectively. Use of any BB was positively associated with recurrence (adjusted HR=1.3, 95% CI: 1.1, 1.5) and the association persisted for non-combination BB prescriptions (adjusted HR=1.3, 95%CI: 1.1, 1.6). When we examined specific BB, associations for exclusive use of propranolol, atenolol, bisoprolol, and carvedilol were near-null and measured with good precision. Exclusive use of metoprolol and sotalol were positively associated with recurrence (for metoprolol, adjusted HR=1.5, 95% CI: 1.2, 1.8; for sotalol, adjusted HR=2.0, 95% CI: 0.99, 4.0). No category of exposure to ACEi or ARB was associated with recurrence. Conclusions: Our findings do not support the hypothesis that BB, ACEi, or ARBs reduce breast cancer recurrence risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5492. doi:1538-7445.AM2012-5492