title: Beta blockers and angiotensin-converting enzyme inhibitors' purported benefit on breast cancer survival may be explained by aspirin use.
abstract: Preclinical and epidemiologic evidence supports a possible role for beta-adrenergic blocking drugs (beta-blockers), and angiotensin-converting enzyme inhibitors (ACEIs) in promoting survival after breast cancer. However, these drugs are often used concurrently with aspirin, and there is a growing body of evidence indicating a survival benefit for aspirin. Therefore, we analyzed the use of beta-blockers and ACEIs after a breast cancer diagnosis and their association with breast cancer mortality, both individually, combined with each other, and in combination with aspirin use in the Nurses' Health Study, using updated measures of medication use and Cox proportional hazards models. There were 4,661 women with stages I-III breast cancer included; 292 breast cancer deaths occurred during median follow-up time of 10.5 years. Modeled individually, the multivariable relative risk and 95 % confidence intervals (RR, 95 % CI) for breast cancer death were (0.76, 0.54-1.05) for beta blockers, (0.89, 0.60-1.32) for ACEIs, and (0.46, 0.35-0.60) for aspirin. Modeled simultaneously, the multivariable (RR, 95 % CI) for breast cancer death were (0.83, 0.60-1.16) for beta blockers, (1.00, 0.68-1.46) for ACEIs, and (0.46, 0.35-0.61) for aspirin. We did not see a significant association with beta blockers and survival, but there was a suggestion. Our study was limited in that we could not assess type of beta blocker and the number of events among users was still quite low. We found no evidence of a protective effect for ACEIs. The strong protective association with aspirin use confounds the associations with these other drugs and underscores the importance of considering aspirin use in analyses of breast cancer survival.
authors: The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. michelle.holmes@channing.harvard.edu
authors: Michelle D
authors: MD
authors: Holmes
authors: Susan E
authors: SE
authors: Hankinson
authors: Diane
authors: D
authors: Feskanich
authors: Wendy Y
authors: WY
authors: Chen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000401:mortality; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D014408:Biomarkers, Tumor; D001241:Aspirin
references: Nat Rev Cancer. 2006 Mar;6(3):240-8
references: 16498446
references: Breast Cancer Res Treat. 2007 Jan;101(2):191-7
references: 16823508
references: Lancet Oncol. 2012 May;13(5):518-27
references: 22440112
references: Breast Cancer Res. 2012 Dec 10;14(6):216
references: 23227958
references: J Cancer Res Clin Oncol. 1990;116(3):303-6
references: 2164516
references: Cancer Res. 2003 Feb 1;63(3):573-8
references: 12566298
references: Lancet. 2012 Apr 28;379(9826):1591-601
references: 22440947
references: Oncotarget. 2010 Nov;1(7):628-38
references: 21317458
references: Breast Cancer Res Treat. 2011 Sep;129(2):549-56
references: 21479924
references: Pharmacol Ther. 2011 May;130(2):177-90
references: 21277894
references: J Clin Oncol. 2011 Jul 1;29(19):2645-52
references: 21632501
references: Gynecol Oncol. 2008 Jun;109(3):418-25
references: 18395779
references: J Cell Physiol. 2003 Aug;196(2):370-7
references: 12811831
references: J Cell Physiol. 2010 Oct;225(1):168-73
references: 20458733
references: J Clin Oncol. 2010 Mar 20;28(9):1467-72
references: 20159825
references: Breast Cancer Res Treat. 2011 Nov;130(2):657-62
references: 21728052
references: J Clin Oncol. 2011 Jul 1;29(19):2635-44
references: 21632503
references: Cancer Invest. 2011 Nov;29(9):585-93
references: 21936625
references: Cancer Causes Control. 2007 Aug;18(6):613-20
references: 17404892
references: Carcinogenesis. 2005 Feb;26(2):459-64
references: 15498791
references: Cancer Res. 2010 Sep 15;70(18):7042-52
references: 20823155