Use of beta-Blockers, Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Risk of Breast Cancer Recurrence: A Danish Nationwide Prospective Cohort Study

• Type of Material: Article
• Authors: Gitte Vrelits Sorensen, Aarhus University; Patricia A. Ganz, University of California Los Angeles; Steven W. Cole, University of California Los Angeles; Lars A. Pedersen, Aarhus University; Henrik Toft Sorensen, Aarhus University; Deirdre P. Cronin-Fenton, Aarhus University; Jens Peter Garne, Aalborg University Hospital; Peer M. Christiansen, Aarhus University; Timothy Lash, Emory University; Thomas P. Ahern, Aarhus University
• Language: English
• Date: 2013-06-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2013 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2012.43.9190
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 31
• Issue: 18
• Start Page: 2265
• End Page: 2278
• Grant/Funding Information: Supported by the National Cancer Institute at the National Institutes of Health (Grants No. R01 CA118708 and T32 CA09001-35); Danish Cancer Society (Grant No. DP06117); Karen Elise Jensen Foundation; the Danish Agency of Science, Technology and Innovation; and the Danish Medical Research Foundation (Grant No. DOK1158859).
• Keywords: Cells; Cooperative group; Norepinephrine; Science & Technology; System; Trials; Survival; ACE-inhibitors; Therapy; Oncology; Mortality; Life Sciences & Biomedicine; Blockade
• Research Categories: Biology, Cell; Health Sciences, Oncology; Health Sciences, Rehabilitation and Therapy

Abstract

Purpose: To estimate associations between use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs) and breast cancer recurrence in a large Danish cohort. Patients and Methods: We enrolled 18,733 women diagnosed with nonmetastatic breast cancer between 1996 and 2003. Patient, treatment, and 10-year recurrence data were ascertained from the Danish Breast Cancer Cooperative Group registry. Prescription and medical histories were ascertained by linkage to the National Prescription Registry and Registry of Patients, respectively. β-Blocker exposure was defined in aggregate and according to solubility, receptor selectivity, and individual drugs. ACE inhibitor and ARB exposures were defined in aggregate. Recurrence associations were estimated with multivariable Cox regression models in which time-varying drug exposures were lagged by 1 year. Results: Compared with never users, users of any β-blocker had a lower recurrence hazard in unadjusted models (unadjusted hazard ratio [HR] = 0.91; 95% CI, 0.81 to 1.0) and a slightly higher recurrence hazard in adjusted models (adjusted HR = 1.3; 95% CI, 1.1 to 1.5). Associations were similar for exposures defined by receptor selectivity and solubility. Although most individual β-blockers showed no association with recurrence, metoprolol and sotalol were associated with increased recurrence rates (adjusted metoprolol HR = 1.5, 95% CI, 1.2 to 1.8; adjusted sotalol HR = 2.0, 95% CI, 0.99 to 4.0). ACE inhibitors were associated with a slightly increased recurrence hazard, whereas ARBs were not associated with recurrence (adjusted ACE inhibitor HR = 1.2, 95% CI, 0.97 to 1.4; adjusted ARBs HR = 1.1, 95% CI, 0.85 to 1.3). Conclusion: Our data do not support the hypothesis that β-blockers attenuate breast cancer recurrence risk.