Changes in Vascular Function and Correlation with Cardiotoxicity in Women with Newly Diagnosed Breast Cancer

Abstract

The objective of this study was to assess the effect of HER2-directed therapy (HER2-Tx) on peripheral vasoreactivity and its correlation with cardiac function changes and the additive effects of anthracycline/cyclophosphamide (AC) therapy and baseline cardiovascular risk. Single-center, prospective cohort study of women with newly diagnosed stage 1-3 HER2-positive breast cancer undergoing HER2-Tx +/- AC. All participants underwent baseline and three-monthly evaluations with Endo-Peripheral Arterial Tonometry (Endo-PAT), vascular biomarkers (C-type natriuretic peptide (CNP) and neuregulin-1 beta (NRG-1β)), and echocardiography. Cardiotoxicity was defined as a decrease in the left ventricular ejection fraction (LVEF) of >10% to a value <53%. Of the 47 patients enrolled, 20 (43%) received AC in addition to HER2-Tx. Deterioration of reactive hyperemia index (RHI) on Endo-PAT by ≥20% was more common in patients receiving HER-Tx plus AC than HER2-Tx alone (65% vs 22%; p=0.003). A decrease in CNP and log NRG-1β levels by 1 standard deviation did not differ significantly between the AC and non-AC groups (CNP: 20.0% vs 7.4%; p=0.20 and NRG-1β: 15% vs 11%; p=0.69) nor did GLS (35% vs 37%; p=0.89). Patients treated with AC had a significantly lower 3D GE LVEF than non-AC recipients as early as 3 months after exposure (mean 59.3 % (SD 3) vs. 63.8 (SD 4); p=0.02). RHI and GLS were the only parameters correlating with LVEF change. Combination therapy with AC, but not HER2-Tx alone, leads to a decline in peripheral vascular and cardiac function. Larger studies will need to define more precisely the causal correlation between vascular and cardiac function changes in cancer patients.