Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience

J Clin Oncol. 2006 Sep 1;24(25):4107-15. doi: 10.1200/JCO.2005.04.9551. Epub 2006 Aug 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Endocardium / drug effects
  • Endocardium / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Failure / chemically induced
  • Heart Failure / physiopathology
  • Humans
  • Microscopy, Electron
  • Middle Aged
  • Odds Ratio
  • Receptor, ErbB-2 / metabolism*
  • Risk Assessment
  • Stroke Volume / drug effects
  • Texas
  • Time Factors
  • Trastuzumab
  • Treatment Outcome
  • Up-Regulation


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptor, ErbB-2
  • Trastuzumab