Abstract: Objective The aim of current study was to evaluate the effect of growth differentiation factor 15(GDF-15)on predicting and monitoring the cardiotoxicity of epirubicin/cyclophosphamide-docetaxel-trastuzumab(EC-D-T)in the treatment of HER-2 positive breast cancer patients.Methods Seventy-three patients with HER-2 positive breast cancer who received EC-D-T adjuvant therapy were enrolled.Serum levels of GDF-15,cardiac troponin I(cTnl)and amino terminal brain natriuretic peptide precursor(NT-proBNP)were measured before adjuvant therapy(M0)and after adjuvant therapy at 3 months(M₃),6 months(M₆),9 months(M₉),12 months(M₁₂)and 15 months(M₁₅).At the same time,patients underwent echocardiography at various time points to assess the left ventricular ejection fraction(LVEF).The cardiotoxicity of this study was defined as:(1)LVEF level decreased by ≥10% after treatment and the absolute value of LVEF was below 53%(normal);(2)heart failure,acute coronary syndrome or severe life-threatening heart rate abnormal.Results After initiation of EC-D-T treatment,the level of LVEF gradually decreased.During the whole study,a total of 21(28.8%)patients developed cardiotoxicity.At the same time,patients with cardiotoxicity had significantly higher levels of GDF-15 at M0 and cTn1 at various time points than those without cardiotoxicity.The level of ProBNP was comparable to those without cardiotoxicity.In addition,Univariate logistic regression analysis showed that baseline GDF-15 might affect the risk of cardiotoxicity. Multivariate logistic regression analysis showed that only cTnl level was an independent predictor for the risk of cardiotoxicity, while NT-proBNP level did not predict the risk of cardiotoxicity.Conclusion The incidence of cardiotoxicity in patients with HER-2 positive breast cancer after receiving EC-D-T is high,and GDF-15 can predict and monitor the risk of cardiotoxicity.

Key words: HER-2 positive breast cancer, Cardiotoxicity, Trastuzumab, GDF-15, Risk