Originally published as JCO Early Release 10.1200/JCO.2005.04.9551 on August 14 2006

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Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience

Valentina Guarneri, Daniel J. Lenihan, Vicente Valero, Jean-Bernard Durand, Kristine Broglio, Kenneth R. Hess, Laura Boehnke Michaud, Ana M. Gonzalez-Angulo, Gabriel N. Hortobagyi, Francisco J. Esteva

From the Departments of Breast Medical Oncology, Cardiology, Biostatistics and Applied Mathematics, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Francisco J. Esteva, Department of Breast Medical Oncology, Unit 1354, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: festeva{at}mdanderson.org

Purpose To evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) –overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX).

Patients and Methods Among 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF).

Results The median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up.

Conclusion The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

published online ahead of print at www.jco.org on August 14, 2006

Supported in part by the Nellie B. Connally Breast Cancer Research Fund.

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

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