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Minimizing Cardiotoxicity While Optimizing Treatment Efficacy with Trastuzumab: Review and Expert Recommendations

^aDepartment of Medical Oncology, San Carlos University Hospital, Madrid, Spain; ^bMD Anderson Cancer Center, Houston, Texas, USA; ^cDepartment of Oncology, Vírgen de la Victoria University Hospital, Málaga, Spain; ^dDepartment of Cardiovascular Diseases, Mayo Clinic, Scottsdale, Arizona, USA; ^eDepartment of Cardiology, San Carlos University Hospital, Madrid, Spain

Key Words. Key Words. • Breast cancer • Cardiotoxicity • Heart failure • Left ventricular ejection fraction • Trastuzumab

Correspondence: Correspondence: Miguel Martín, M.D., Ph.D., Department of Medical Oncology, Hospital Clínico San Carlos, Profesor Martín Lago s/n, 28040 Madrid, Spain. Telephone: 34-91-3303546; Fax: 34-91-3303544; e-mail: mmartin{at}geicam.org

Received June 18, 2008; accepted for publication December 1, 2008.

Disclosures: Miguel Martín: Honoraria: Roche; Francisco J. Esteva: Honoraria: Roche; Emilio Alba: Honoraria: Roche; Bijoy Khandheria: Honoraria: Roche; Leopoldo Pérez-Isla: Honoraria: Roche; José Ángel García-Sáenz: Honoraria: Roche; Antonia Márquez: Honoraria: Roche; Partho Sengupta: None; José Zamorano: Honoraria: Roche

Section editors Gabriel N. Hortobágyi and Kathleen I. Pritchard have disclosed no financial relationships relevant to the content of this article.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.

Numerous clinical studies have demonstrated the therapeutic benefit of trastuzumab in women with breast cancer. However, a small but not insignificant proportion of patients have experienced trastuzumab-associated cardiotoxicity during these trials. This phenomenon is generally characterized by an asymptomatic reduction in left ventricular ejection fraction (LVEF) or, less often, congestive heart failure (CHF). Concomitant anthracycline therapy significantly increases the risk for cardiotoxicity during trastuzumab treatment, and such regimens are therefore not recommended. The cardiac dysfunction associated with trastuzumab is most often reversible upon discontinuation of treatment and initiation of standard medical therapy for CHF.

Prior to treatment initiation, a risk–benefit analysis should be performed for each individual patient, including a thorough assessment of potential risk factors and cardiac function. Cardiac monitoring should be continued throughout trastuzumab therapy and the follow-up period, because early recognition of trastuzumab-associated cardiac dysfunction can allow effective medical intervention. Following the occurrence of asymptomatic LVEF reduction or CHF and appropriate medical intervention, reintroduction of trastuzumab may be considered in patients following resolution of normal cardiac function, or in those for whom the benefit of antitumor therapy outweighs the risk for CHF.