超敏肌钙蛋白I和N末端B型钠尿肽原对曲妥珠单抗致心脏毒性的预测价值

Value of hs-cTnI and NT-proBNP in prediction of trastuzumab-induced cardiotoxicty

目的评估超敏肌钙蛋白I(high-Sesitivity troponin I,hs-c Tn I)和N末端钠尿肽原(N terminal brain natriuretic peptide,NT-pro BNP)对曲妥珠单抗致心脏毒性的预测价值。方法收集117例医院接受蒽环类化疗药物序贯曲妥珠单抗治疗的乳腺癌患者的病例资料,在蒽环类化疗前(visit1)和曲妥珠单抗用药前(visit2)、曲妥珠单抗治疗开始的3个月(visit3)及随后每3个月1次进行全面的心脏检查和超声心动图评估心功能。在visit1、visit2和visit3检测hs-c Tn I和NT-pro BNP的浓度,共随访15个月,发生心脏毒性事件为观察终点。根据曲妥珠单抗致心脏毒性的诊断指标,将患者分为心脏毒性组和非心脏毒性组。评价hs-c Tn I和NT-pro BNP对曲妥珠单抗致心脏毒性的预测价值。结果 16例出现心脏毒性,心脏毒性组与非心脏毒性组的hs-c Tn I水平在Visit2和Visit3,两组组间比较有统计学差异(P<0.05),而NT-pro BNP仅在曲妥珠单抗治疗治疗开始3个月两组间比较差异有统计学意义(P<0.01)。以曲妥珠单抗治疗开始3个月的血清hs-c Tn I和NT-pro BNP浓度水平进行ROC曲线分析,可见hs-c Tn I的AUC、特异度和敏感性都很高,且均优于NT-pro BNP,故可认为,hs-c Tn I是一个曲妥珠单抗致心脏毒性的预测生物标志物。

Objective To evaluate the predictive value of cardiac troponin I（ hs-c Tn I） and N terminal brain natriuretic peptide（ NT-pro BNP） for cardiac toxicity induced by trastuzumab. Methods Clinical data on 117 patients with breast cancer treated in our hospital with anthracycline chemotherapy and sequential therapy of trastuzumab was collected. At baseline（ visit1）,before administration of anthracycline（ visit2）,3 months into the administration of trastuzumab and paclitaxel（ visit3）,6 months into the administration of trastuzumab,hs-c Tn I and NT-pro BNP levels were detected. The follow-up was 15 months. Echocardiography and questionnaires were used every three months（ a total of 6 times）. The patients were divided into two groups according to the diagnostic criteria of cardiac toxicity to assess the predictive value of hs-c Tn I and NT-pro BNP in the cardiac toxicity of trastuzumab. Results There were 16 cases of cardiac toxicity. and the difference in hs-c Tn I levels at Visit2 and Visit3 was statistically significant between the cardiac toxicity group and the non cardiac toxicity group（ P〈0. 05）,while levels of NT-pro BNP were significantly different between the two groups only 3 months into trastuzumab treatment（ P〈0. 01）. ROC curve analysis of the serum hs-c Tn I and NT-pro BNP concentrations suggested that the AUC,specificity and sensitivity of hs-c Tn I were quite good. Conclusions hs-c Tn I can serve as a predictive biomarker of cardiac toxicity s induced by trastuzumab.