Prevention of Trastuzumab and Anthracycline-Induced Cardiotoxicity Using Angiotensin-Converting Enzyme Inhibitors or Beta-Blockers in Breast Cancer Patients

Abstract

Objectives: The purpose of this study was aimed to1) examine treatment patterns of anti-neoplastic agents prescribed to breast cancer patients, 2) estimate the incidence of and identify factors associated with adjuvant chemotherapy-induced cardiotoxicity and all-cause mortality among breast cancer patients, and 3) compare the effect of angiotensin-converting enzyme inhibitors and/or β blockers (ACEIs/BBs) in prevention of trastuzumab- and anthracycline-induced cardiotoxicity and all-cause mortality. Methods: A retrospective cross-sectional analysis using the 2006-2010 National Ambulatory Medical Care Survey (NAMCS) data was conducted for aim 1. Breast cancer treatments were categorized. A visit-level descriptive analysis estimated national prescribing trends and multiple logistic regression analyses identified factors associated with anti-neoplastic agent used. Two population-based cohort studies of women newly diagnosed with breast cancer were conducted for aim 2 and 3, using the 2000-2010 Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Adjuvant chemotherapy was classified and ACEIs/BBs exposure group was defined as a filled prescription before/after the initiation of trastuzumab/anthracyclines. Cumulative rates of cardiotoxicity and all-cause mortality were estimated and Cox models and/or marginal structural models were used to determine factors associated with cardiotoxicity and all-cause mortality adjusting for baseline covariates and time-dependent variable, respectively. Results: The proportion of visits in which anti-neoplastic agents were documented remained stable over time. Factors including patient socio-demographics, types of insurance, and cancer stage were associated with types of breast cancer treatment. Next, compared with hormones, risk of cardiotoxicity was higher in patients treated with adjuvant anthracycline and trastuzumab-based, trastuzumab-based, and anthracycline-based regimens, respectively. Risk of all-cause mortality was higher in patients treated with taxane-based regimens compared with hormones. Further, the ACEIs/BBs exposure group had lower risk of cardiotoxicity and all-cause mortality compared to the non-exposed group. Baseline characteristics, including socio-demographics, tumor characteristics, comorbidity, and concomitant treatment were associated with an elevated risk of all-cause mortality and/or cardiotoxicity (all P<0.05) Conclusions: Anti-neoplastic treatment patterns differ among breast cancer patients treated in ambulatory settings. Among breast cancer patients undergoing adjuvant chemotherapy, those treated with trastuzumab-based/anthracycline-based regimens had increased cardiotoxicity risk compared with hormones. An initiation of ACEIs/BBs in those received adjuvant trastuzumab/anthracyclines may prevent cardiotoxicity and improve survival.