Correlation Of Circulating Pro-Angiogenic Micrornas Expressions With Risk Of Cardiotoxicity By Epirubicin/Cyclophosphamide Followed By Docetaxel Adjuvant Chemotherapy In Patients With Breast Cancer

Objective:The aim of our study was to assess the value of circulating 14 pro-angiogenic micro RNAs(mi RNAs)in predicting the risk of cardiotoxicity of epirubicin/cyclophosphamide followed by docetaxel(EC-D)as adjuvant chemotherapy in patients with breast cancer(BC).Methods:This prospective cohort study consecutively enrolled 195 BC patients received EC-D adjuvant chemotherapy.The peripheral blood samples were collected from all participants before the adjuvant chemotherapy(Cycle 0,C0)and plasma was separated from each sample.The expressions of 14 pro-angiogenic mi RNAs in plasma were assessed by quantitative polymerase chain reaction(q PCR),and the level of cardiac troponin I(c Tn I)was determined by immunoenzymatic fluorescent assay.The left ventricular ejection fraction(LVEF)was evaluated by echocardiograph at C0,the end of 4 cycles of EC chemotherapy(C4),the end of 4 cycles of docetaxel chemotherapy(C8)and 3 months,6months,9 months and 12 months post surgery.The cardiotoxicity was defined as the LVEF declined by 10% from baseline to below 55%(the lower limit of normal),heart failure,acute coronary artery syndrome or fatal arrhythmia.Results:The LVEF surprisingly declined at C4(P<0.001)and C8(P<0.001)post EC-D chemotherapy compared to the baseline level,although the LVEF levels were numerically increased at M3-M12,they were still notably decreased compared with baseline.Throughout the follow up time,11(5.6%)patients presented with a LVEF decline of 10%from baseline to below 55%,no patient had heart failure,acute coronary artery syndrome or fatal arrhythmia.The overall cardiotoxicity rate was 5.6%.The levels of let-7f(P=0.027),mi R-20a(P=0.008),mi R-126(P=0.009),mi R-210(P=0.048)and mi R-378(P=0.043)were markedly declined in patients presented with cardiotoxicity.Univariate and multivariate logistic regressions revealed that let-7f(P=0.016),mi R-20a(P=0.047),mi R-126(P=0.025)and mi R-210(P=0.041)were independent predictive factors for the occurrence of cardiotoxicity.Receiver operating characteristics(ROC)curve illuminated that combining let-7f,mi R-20 a,m IR-126 and mi R-210 had a good area under curve(AUC)of 0.887(95%CI: 0.809-0.965)with sensitivity of 77.2% and specificity of 90.9% at the best cut-off point.In addition,the let-7f level(P<0.001)and mi R-20 a level(P=0.001)at C0 were negatively correlated with the level of c Tn I.Conclusion:Circulating let-7f,mi R-20 a,mi R-126 and mi R-210 expressions could be served as biomarkers for predicting low risk of cardiotoxicity by EC-D adjuvant chemotherapy in patients with BC.