Risk of cardiac dysfunction with trastuzumab in breast cancer patients: A meta-analysis

Background: Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment. Methods: We searched PubMed and Web of Science (January 1966-July 2009) and American Society of Clinical Oncology conferences held (January 2000-July 2009) for relevant articles and abstracts. Summary incidence rates, relative risks (RRs), and 95% confident intervals (CIs) were calculated using a fixed-effects or random-effects model. Results: 11,882 patients from 10 RCTs were included for analysis. The incidences of LVEF decrease and congestive heart failure (CHF) were 7.5% (95% CI 4.2-13.1) and 1.9% (95% CI 1.0-3.8) among patients receiving trastuzumab. Trastuzumab significantly increased the risk of LVEF decrease (RR = 2.13, 95% CI, 1.31-3.49; p=0.003). In addition, it significantly increased the risk of CHF (RR=4.19, 95% CI 2.73-6.42; p< 0.00001). The increased risk of CHF was observed in patients with early stage (RR=4.05, 95% CI 2.49-6.58; p< 0.00001) as well as metastatic disease (RR=4.75, 95% CI 1.93-11.71; p=0.0007). Furthermore, trastuzumab significantly increased the risk of CHF (RR=4.27, 95% CI 2.75-6.61, p< 0.00001) in patients receiving anthracycline-based chemotherapy, but not in patients receiving non-anthracycline chemotherapy (RR=2.42, 95% CI 0.36-16.19, p=0.36). Conclusion: The addition of trastuzumab to anthracycline-based chemotherapy significantly increase the risk of cardiac dysfunction in breast cancer patients. Further studies are recommended for non-anthracycline chemotherapy.