Risk factors of trastuzumab-induced cardiotoxicity in breast cancer: A meta-analysis

BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear. This meta-analysis aims to consolidate previously published data to identify the risk factors most likely leading to TIC. METHODS: A search of the MEDLINE literature database using the keywords trastuzumab/Herceptin, risk factors, outcomes, cardiac, cardiotoxicity, cardiomyopathy, LVEF, and chemotherapy was performed. Only prospective/retrospective human studies were included, with additional studies excluded if they reported baseline LVEF > 68%, a cohort of <50 patients, or results that were not stratified based on cardiotoxic events. Pooled odds ratio (OR) and 95% confidence interval (CI) for each potential risk factor were calculated, with heterogeneity of data and samples explored using random-effects modeling. RESULTS: Data were collected from 17 articles, capturing 6527 patients. Hypertension (OR 1.61, 95% CI 1.14–2.26; P < 0.01), diabetes (OR 1.62; 95% CI 1.10–2.38; P < 0.02), previous anthracycline use (OR 2.14; 95% CI 1.17–3.92; P < 0.02), and older age (P = 0.013) were all shown to be associated with TIC. CONCLUSION: Cardiac performance should be closely monitored in women treated with trastuzumab. Recognizing potential risk factors along with careful attention to symptoms/LVEF measurements could minimize the occurrence of TIC in this population.