Correlation of circulating pro-angiogenic miRNAs with cardiotoxicity induced by epirubicin/cyclophosphamide followed by docetaxel in patients with breast cancer

OBJECTIVE: This study aimed to evaluate predictive value of 14 pro-angiogenic miRNAs for cardiotoxicity induced by epirubicin/cyclophosphamide follow by docetaxel (EC-D) in breast cancer (BC) patients. METHODS: Three hundred and sixty-three BC patients receiving EC-D neoadjuvant chemotherapy were consecutively enrolled in this prospective cohort study. Peripheral blood sample was obtained from each patient, and plasma was separated. The expressions of 14 pro-angiogenic miRNAs, cardiac troponin I (cTnI) and N-terminal pro brain natriuretic peptide (NT-proBNP) were evaluated. Left ventricular ejection fraction (LVEF) level at C0, the end of 4 cycles of EC chemotherapy (C4), the end of 4 cycles of docetaxel treatment (C8), 3rd months (M3), 6th months (M6), 9th months (M9) and 12th months (M12) after surgery were assessed. RESULTS: LVEF decreased at C4, C8, M3, M6, M9 and M12 compared with C0, and the total cardiotoxicity incidence was 5.2%. Additionally, the levels of let-7f, miR-17-5p, miR-20a, miR-126, miR-210 and miR-378 were reduced in cardiotoxicity patients. Multivariate logistic regression revealed that miR-17-5p and miR-20a were independently predictive factors for less cardiotoxicity. Receiver operating characteristics (ROC) curve displayed a satisfactory predictive value for lower cardiotoxicity risk with area under curve (AUC) of 0.842 of the combination of the miR-17-5p and miR-20a expressions. In addition, let-7f,miR-126, miR-210 and miR-378 levels negatively correlated with cTnI expression, and let-7f and miR-130a expressions reversely correlated with NT-proBNP level.CONLUSIONS: miR-17-5p and miR-20a could be served as biomarkers for lower cardiotoxicity induced by EC-D neoadjuvant chemotherapy in BC patients.