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Clinical Cardiac Tolerability of Trastuzumab

From the Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL; and the Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN

Address reprint requests to Edith A. Perez, MD, Professor of Medicine, Division of Hematology and Oncology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: perez.edith{at}mayo.edu

PURPOSE: This review provides an update on the current understanding of the clinical cardiac tolerability of trastuzumab, a humanized monoclonal antibody effective in the treatment of patients with advanced breast cancer overexpressing or amplifying HER2.

METHODS AND RESULTS: We produced a summary of currently available information regarding the incidence and natural history of trastuzumab-associated cardiac dysfunction. Data from new, prospective clinical studies that incorporate close cardiac monitoring and standardized follow-up in patients with either advanced or earlier stages of breast cancer are also presented, and hypotheses regarding potential mechanisms of trastuzumab-related cardiotoxicity are discussed. Patients treated with trastuzumab in the pivotal trials were found to have increased risk for cardiac dysfunction, mostly when used concurrent with anthracyclines. Recent trials have required more stringent and consistent cardiac monitoring criteria and excluded patients with abnormal cardiac function, pre-existing heart disease, and/or high cumulative doses of anthracyclines. Decreases of ejection fraction and a few cases of congestive heart failure (CHF) requiring medical therapy have been detected. Improvements in ejection fraction and the symptoms of CHF have been subsequently noted in a significant number of these patients.

CONCLUSION: Trastuzumab is associated with an increased risk of asymptomatic decreases in ejection fraction, and, in a small number of patients, CHF that is almost always responsive to medical management. This risk is greatest in patients receiving concurrent anthracyclines. More data are needed to help elucidate the pathophysiology of this syndrome.

Supported in part by grants from the National Cancer Institute (CA 25224-215 5B4935), Genentech Inc, and the Breast Cancer Research Foundation, New York, NY.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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