Association of cardiovascular disease risk factors with late cardiotoxicity and survival in HER2-positive breast cancer survivors

Purpose: Breast cancer and cardiovascular diseases often share the same risk factors. It is increasingly important to identify risk factors for cardiovascular (CV) events in high-risk breast cancer patients and explore optimal treatment regimens. Patients and Methods: Early HER2-positive breast cancer patients at our institution between January 1998 and October 2009 were reviewed. Primary outcome was late-severe-CV-event–free survival, and late severe CV events were defined as cardiovascular death, cardiomyopathy, symptomatic heart failure and myocardial infarction developing 2+ years after breast cancer diagnosis. Kaplan-Meier plots, Cox proportional hazard regressions, and restricted mean survival time were used to evaluate outcomes. Results: We identified 2,448 consecutive eligible patients with a median follow-up time of 111.0 months (interquartile range, 52.0–151.8 months). 136 patients had late severe CV events and 752 died of any cause (533 (70.9%) died of primary breast cancer; 12 (1.6%) died of cardiovascular disease). Hypertension (hazard ratio [HR], 1.546; 95% confidence interval [95%CI], 1.030–2.320; P=0.036) and history of coronary artery disease (CAD) (HR, 3.333; 95%CI, 1.669–6.656; P<0.001) were associated with worse late-severe-CV-event–free survival. Anthracycline-containing regimens (HR, 1.536; 95%CI, 0.979–2.411; P=0.062) was not a significant risk factor for CV events in multivariate analysis. Regimens containing both anthracycline and anti-HER2 therapy were prognostic for better OS (HR, 0.515; 95%CI, 0.412–0.643; P<0.001). Conclusions: Hypertension and CAD history were independent prognostic factors for late severe CV events. Adding anti-HER2 agents to anthracycline-containing regimens did not substantially increase the risk for late severe cardiotoxicity and conferred better overall survival.