Beta blockers and angiotensin-converting enzyme inhibitors’ purported benefit on breast cancer survival may be explained by aspirin use
- 464 Downloads
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.
KeywordsAdrenergic beta-antagonists Angiotensin-converting enzyme inhibitors Aspirin Breast neoplasms Survival
We wish to thank Gideon Aweh for his computer programing assistance. In addition, we would like to thank the participants and staff of the Nurses’ Health Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by the National Institutes of Health grant CA87969. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. The authors have no further financial relationship with the funder, and no conflicts of interest to declare, with the exception of Dr. Holmes, who has received remuneration from Trulife.com. The authors have full control of all primary data and the Journal may review the data if requested.
This work was approved by the Institutional Review Board of the Brigham and Women’s Hospital, Boston MA, and complies with all U.S. laws regarding human subjects.
- 4.Sloan EK, Priceman SJ, Cox BF, Yu S, Pimentel MA, Tangkanangnukul V, Arevalo JM, Morizono K, Karanikolas BD, Wu L, Sood AK, Cole SW (2010) The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res 70(18):7042–7052. doi: 10.1158/0008-5472.CAN-10-0522 PubMedCrossRefGoogle Scholar
- 7.Melhem-Bertrandt A, Chavez-Macgregor M, Lei X, Brown EN, Lee RT, Meric-Bernstam F, Sood AK, Conzen SD, Hortobagyi GN, Gonzalez-Angulo AM (2011) Beta-blocker use is associated with improved relapse-free survival in patients with triple-negative breast cancer. J Clin Oncol 29(19):2645–2652. doi: 10.1200/JCO.2010.33.4441 PubMedCrossRefGoogle Scholar
- 8.Ganz PA, Habel LA, Weltzien EK, Caan BJ, Cole SW (2011) Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort. Breast Cancer Res Treat. doi: 10.1007/s10549-011-1505-3
- 13.Greco S, Muscella A, Elia MG, Salvatore P, Storelli C, Mazzotta A, Manca C, Marsigliante S (2003) Angiotensin II activates extracellular signal regulated kinases via protein kinase C and epidermal growth factor receptor in breast cancer cells. J Cell Physiol 196(2):370–377. doi: 10.1002/jcp.10313 PubMedCrossRefGoogle Scholar
- 16.Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE (2010) Aspirin intake and survival after breast cancer. J Clin Oncol. doi: 10.1200/JCO.2009.22.7918
- 20.Algra AM, Rothwell PM (2012) Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. doi: 10.1016/S1470-2045(12)70112-2