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).


CONCLUSIONS
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.
Chen
Tao
T
Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
Xu
Tao
T
Li
Yang
Y
Liang
Chun
C
Chen
Juxiang
J
Lu
Yicheng
Y
Wu
Zonggui
Z
Wu
Shenhong
S
D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016275:Atrial Function / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D014943:Global Health; D006331:Heart Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D012307:Risk Factors; D000068878:Trastuzumab; D016276:Ventricular Function / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068878:Trastuzumab