Background Trastuzumab is life-extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 ( HER 2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline. Methods and Results We performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre- and on-therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function ( LVEF 63.4±5%) and 20 had an impaired cardiac function ( LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF , compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation ( P= NS ). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P<0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF ( P<0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%. Conclusions Women undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co-managed by a cardiologist.
Keywords: HER2; breast cancer; cardiomyopathy; cardiotoxicity; chemotherapy; heart failure; left ventricular ejection fraction; trastuzumab; treatment.