| Objective As a targeted therapeutic drug,trastuzumab has been approved in the treatment of metastatic and early breast cancer since 1988.At present,one-year auxiliary treatment of trastuzumab for HER2-postive early breast cancer patients has been standardized to significantly elevate the overall survival,which made breast cancer as a chronic disease.However,there are more and more reports on cardiotoxicity induced by trastuzumab.The hidden onset and late discovery of cardiotoxicity always result in cardiac insufficiency or failure,which are the death causes in patients survived from breast cancer.LVEF is the most common indicator for evaluation of cardiotoxicity during anti-neoplastic treatment,and more studies indicate the cardiac damages due to myocyte necrosis happened long before the reduction of insensitive LVEF.The recognition of early changes in cardiac structure and funtion is the critical process during preventing cardiotoxicity in late stages.Although researchers have made progresses in early sensitive indicators of cardiac subclinical injuries and found the close relationship between biomarkers and cardiotoxicity,which one can be applied to the early prediction of the cardiotoxicity incidence during anti-neoplastic treatment remains unclear.This study aimed to detect the levels of hs-cTnI,T?4 and NT-proBNP,in order to discuss their clinical value in predicting cardiotoxicity induced by trastuzumab and chemotherapy.Method Breast cancer patients diagnosed as her-2 positive and received AC-TH auxiliary chemotherapy at our hospital(2013-2015)were prospectively recruited according to inclusion and exclusion criteria.The levels of hs-cTnI,T?4 and NT-proBNP were measured during visit 1(baseline,before anthracyclines),visit 2(3months,before using trastuzumab and taxane)and visit 3(6 months,during using trastuzumab).Fifteen months from the baseline,echocardiography and questionnaires were implemented every three months(a total of 6 times).SPSS19.0software was utilized to analyze data,the measurement data was described by summary,average and standard deviation,enumeration data was displayed by percentage and rate.Comparative methods for pathological information were t-test for continuous variables and chi-square test for classified variables.The incidence of cardiotoxicity was set as outcome event.For a concise description,the dynamic variance in cTnI,T?4 and NT-proBNP during visit 1 to visit 3 were respectively displayed as ?hs-cTnI,?T?4and ?NT-proBNP.Then the predictive value of these combined biomarker detection on subsequent cardiotoxicity was clarified.By ROC curve,the predictive values of cTnI,T?4 and NT-proBNP were compared.Then the indictors with higher significance was applied to COX survival analysis,and divided in to two-high group(two indicators both higher than the threshold)and one-high group(one indicator higher than the threshold).These two groups were assigned to 1 and 0 as new variables in further COX survival analysis.Result A total of 129 HER-2 positive early breast cancer patients were recruited,and the longest follow-up visit lasted for 15 months.Due to changing chemotherapy plan,losing telephone follow-up and missing critical indicator,the study was based on117 subjects excluding 12 cases.Patients aged from 24 to 75 with an average of47.95±8.94.There were 16 cardiotoxicity cases(13.67%)with the median time of 9.8months(inter-quartile range of 2 to 15).The median of LVEF change in cardiotoxicity patients was 15.35%(inter-quartile range of 12.57% to 19.19%),including 3 cases LVEF reduction from ?5% to <55% with symptom and sign of CHF.For the other 13 cases,there were 11 case reduced ?10% to <55% with no symptom and sign of CHF,and 2 cases reduced ?10% <55% with certain symptom and sign.According to the incidence of cardiotoxicity,the patients were divided into cardiotoxicity group andnon-cardiotoxicity group,and no statistical difference was found in general pathological information at baseline(P>0.05).In the comparison in the dynamic variance of biomarkers before and after chemotherapy,hs-ctnI and T?4 were significantly and positively correlated to subsequent cardiac damages,and the changes of hs-cTnI concentration was earlier than T?4.Meanwhile,the concentration change of NT-proBNP was not significantly related to cardiotoxicity.AUC of ROC curve indicated 0.964 and 0.930 for hs-cTnI and T?4 respectively,and significantly statistical difference was found towards 0.500(P<0.01);AUC of NT-proBNP ROC was0.656,which was statistical significant to 0.500(P<0.05).The descending order was hscTnI> T?4>NT-proBNP,indicating little predictive value of NT-proBNP for cardiotoxicity.In the risk ratio analysis of combined detection of hs-cTnI and T?4 or single indictor,the risk of subsequent cardiotoxicity in two-high group was 9.486-fold of that in one-high group(HR=9.486),which indicated combined detection was more efficient in the prediction of cardiotoxicity induced by trastuzumab.Conclusion This study certified the early breast cancer patients who received trastuzumab and antharcycline chemotherapy1.hs-cTnl and T?4 were the sensitive indicators in early injuries of cardiotoxicity excluding NT-proBNP;2.In the comparison between indicators,hs-cTnl had the most superior predictive value of cardiotoxicity to T?4 for its availability in early stages;3.In the comparision between single and combined indicators values,the combined detection of hs-cTnI and T?4 was more favorable than single indictor,which effectively recognized the patients with high risk of cardiotoxicity during the subsequent year. |
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