Conventional cardiac risk factors associated with trastuzumab-induced cardiotoxicity in breast cancer: Systematic review and meta-analysis.

BACKGROUND: Trastuzumab has had a major impact on the treatment of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. However, it is associated with cardiotoxicity, expressed as an asymptomatic decrease in left ventricular ejection fraction (LVEF) and less often as clinical HF. The aim of this meta-analysis is to identify the association of conventional cardiovascular risk factors with the development of trastuzumab-induced cardiotoxicity (TIC). METHODS: A literature search of PubMed was conducted to identify studies examining the association between cardiovascular risk factors and TIC. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated examining the odds of developing TIC for each of the risk factors. RESULTS: A total of 35 studies were included in the analysis. Age (OR:0.7; 95%CI 0.318-1.09; P= 0.0004), hypertension (OR:0.69; 95%CI 0.26-1.12; P = 0.001), smoking(OR:0.35; 95%CI 0.01- 0.69; P = 0.038), diabetes mellitus (OR:0.44; 95%CI 0.24- 0.68; P = 0.0001) and family history of CAD (OR:5.51, 95%CI 1.76-17.25; P< 0.00001)were significantly associated with the development of cardiotoxicity. Known history of CAD (OR: 3.72; 95%CI 2.11-6.57; P = 0.0005) was also associated with the development of TIC. CONCLUSION(S): Identifying women at risk for TIC have several important potential applications. Clinicians may decide to assess LVEF more frequently in patients at highest risk for TIC in order to detect LV systolic dysfunction earlier. Additionally, this could help identify patients who would benefit most from prophylactic therapy for preventing TIC.