Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients

Abstract

Breast cancer is the most frequently occurring cancer among women worldwide. Human epidermal growth factor receptor 2 (HER2 or ErbB2) is overexpressed in between 20 and 25% of invasive breast cancers and is associated with poor prognosis. Trastuzumab, an anti-ErbB2 monoclonal antibody, reduces cancer recurrence and mortality in HER2-positive breast cancer patients, but unexpectedly induces cardiac dysfunction, especially when used in combination with anthracycline-based chemotherapy. Novel approved ErbB2-targeting drugs, including lapatinib, pertuzumab, and trastuzumab-emtansine, also potentially cause cardiotoxicity, although early clinical studies demonstrate their cardiac safety profile. Unfortunately, the mechanism involved in causing the cardiotoxicity is still not completely understood. In addition, the use of preventive interventions against trastuzumab-induced cardiac dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, remain controversial. Thus, this review aims to summarize and discuss the evidence currently available from in vitro, in vivo, and clinical studies regarding the mechanism and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs.