Beta blockers and angiotensin-converting enzyme inhibitors’ purported benefit on breast cancer survival may be explained by aspirin use

Michelle D. Holmes, Susan E. Hankinson, Diane Feskanich, Wendy Y. Chen

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.