Early Decline in Left Ventricular Ejection Fraction Can Predict Trastuzumab-Related Cardiotoxicity in Patients with Breast Cancer: A Study Using 13 Years of Registry Data

PURPOSE: While concerns regarding trastuzumab-related cardiac dysfunction (TRCD) in patients with breast cancer are increasing, there is a lack of evidence supporting the current recommendations for TRCD monitoring. We aimed to investigate the clinical predictors of TRCD in the adjuvant setting of human epidermal growth factor receptor 2–positive breast cancer patients. MATERIALS AND METHODS: From August 2003 to April 2016, consecutive 998 patients who were treated with adjuvant trastuzumab for breast cancer were retrospectively evaluated. TRCD was defined as a decrease ≥10% in left ventricular ejection fraction (LVEF), with a decline below the normal limit or symptomatic heart failure. RESULTS: Among 787 eligible patients who had complete data sets consisting of both baseline and follow-up assessment of left ventricular systolic function by echocardiography (mean age, 49.9±9.5 years), 58 (7.4%) developed TRCD. TRCD patients had lower baseline LVEF (63% [59–66] vs. 65% [61–68], p=0.016) and more frequently administered Adriamycin (98% vs. 89%, p=0.022) than those without TRCD. On follow-up echocardiography, a drop in LVEF ≥5% within the first 3 months was more frequent in TRCD patients (78.3% vs. 38.4%, p<0.001). Regardless of baseline LVEF and Adriamycin treatment, a drop in LVEF ≥5% within the first 3 months of trastuzumab administration was strongly associated with the development of TRCD (adjusted hazard ratio, 45.1[17.0–127.6], p<0.001). CONCLUSION: The overall incidence of TRCD was 7.4% in Asian breast cancer patients treated with adjuvant trastuzumab. A decline in LVEF ≥5% within the first 3 months of trastuzumab initiation was strongly associated with TRCD development in patients with breast cancer.