Cardiac safety analysis of anti-HER2-targeted therapy in early breast cancer

Abstract

To evaluate the cardiac safety of anti-HER2-targeted therapy for early breast cancer; to investigate whether trastuzumab combined with pertuzumab increases cardiac toxicity compared with trastuzumab; to evaluate the predictive value of high-sensitivity Troponin (hs-TnI) and QTc for the cardiotoxicity associated with anti-HER2 targeted therapy in early breast cancer. A total of 420 patients with early-stage HER2-positive breast cancer who received trastuzumab or trastuzumab combined with pertuzumab for more than half a year in Tianjin Medical University Cancer Hospital from January 2018 to February 2021 were included. Left ventricle ejection fraction (LVEF), hs-TnI values, and QTc were measured at baseline and 3, 6, 9, 12 months. Cardiotoxicity was defined as a decrease in LVEF of at least 10 percentage points from baseline on follow-up echocardiography. Cardiotoxicity developed in 67 of the 420 patients (15.9%) and all patients had LVEF above 50% before and after treatment. The incidence of cardiotoxicity in trastuzumab and trastuzumab combined with pertuzumab was 14.3% and 17.9%, respectively (P > 0.05). Logistic regression analysis showed that age, coronary heart disease, left chest wall radiotherapy, and anthracyclines sequential therapy were independent risk factors for cardiotoxicity (P < 0.05). The value of hs-TnI and QTc at the end of treatment (12th month) were selected for ROC curve prediction analysis and the area under the ROC curve was 0.724 and 0.713, respectively, which was significantly different from the area of 0.5 (P < 0.05). The decrease of LVEF in the study was mostly asymptomatic, from the heart safety point of view, the anti-HER2 targeted therapy for early breast cancer was well tolerated. Trastuzumab combined with pertuzumab did not significantly increase cardiotoxicity. However, subgroup analysis suggests that in the presence of coronary artery disease (CAD) and sequential treatment with anthracene, trastuzumab and pertuzumab may increase the cardiac burden compared with trastuzumab. Hs-TnI and QTc may be useful in monitoring and predicting cardiotoxicity associated with anti-HER2 targeted therapy for early breast cancer.