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Cardiotoxicity of trastuzumab and other HER2-targeted agents

James P Morgan, MD, PhD
Section Editor
Daniel F Hayes, MD
Deputy Editor
Sadhna R Vora, MD


Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor-2 (HER2, also ErbB2). For the 15 to 20 percent of patients with breast cancer whose tumors overexpress HER2, trastuzumab therapy is important in the treatment of both early and advanced disease. Its use, however, results in a small to modest risk for cardiotoxicity, which is typically manifested by an asymptomatic decrease in left ventricular ejection fraction and less often by clinical heart failure. (See "Adjuvant systemic therapy for HER2-positive breast cancer", section on 'Trastuzumab-based therapy' and "Systemic treatment for HER2-positive metastatic breast cancer".)

Following the introduction of trastuzumab, three other HER2-targeted agents have been developed for treatment of HER2-overexpressing breast cancer: lapatinib, a small molecule dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR; ErbB1; HER1) and HER2; ado-trastuzumab emtansine (also known as T-DM1), an antibody-drug conjugate composed of trastuzumab, a thioether linker, and a derivative of the antimitotic agent, maytansine; and pertuzumab, a monoclonal antibody that binds subdomain II of the HER2 extracellular domain and prevents HER2 homo- and heterodimerization with other HER-family receptors. Although data are limited on pertuzumab and T-DM1, the available data support the view that these agents may be less cardiotoxic than trastuzumab. (See "Systemic treatment for HER2-positive metastatic breast cancer".)

Cardiotoxicity related to trastuzumab and related HER2-targeted agents will be presented here. The cardiotoxicity of other antineoplastic drugs, including anthracyclines and taxanes, management of heart failure, and clinical use of trastuzumab and other HER2-targeted therapies are discussed separately.

(See "Clinical manifestations, monitoring, and diagnosis of anthracycline-induced cardiotoxicity".)

(See "Prevention and management of anthracycline cardiotoxicity".)

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Literature review current through: Nov 2017. | This topic last updated: Mar 28, 2017.
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