曲妥珠单抗联合化疗致心脏毒性的影响因素分析

Analysis of influential factors of cardiotoxicity induced by trastuzumab combined with chemotherapy

目的 分析曲妥珠单抗联合化疗致人表皮生长因子受体2(HER-2)阳性乳腺癌患者心脏毒性的影响因素。方法 选取在我院2017年4月-2021年1月接受吡柔比星+环磷酰胺序贯紫杉醇+曲妥珠单抗治疗的HER-2阳性乳腺癌患者200例,根据有无发生心脏毒性分为发生心脏毒性组和未发生心脏毒性组。收集患者的临床资料及超声心动图检查结果,分析患者发生心脏毒性的影响因素。结果 200例乳腺癌患者中,发生心脏毒性的有43例,发生率为21.5%。其中,吡柔比星+环磷酰胺治疗期间出现心脏毒性的患者占5.5%(11/200),序贯紫杉醇+曲妥珠单抗治疗期间出现心脏毒性的患者占20.5%(41/200),后者显著高于前者(P<0.01)。同时,序贯紫杉醇+曲妥珠单抗治疗期间患者左室射血分数降低幅度显著高于吡柔比星+环磷酰胺治疗期间[14%(12%,17%)vs. 7%(3%,10%),P<0.001]。与未发生心脏毒性的患者相比,发生心脏毒性患者中有高脂血症史的占比显著升高(P<0.01),而使用右雷佐生的占比显著降低(P<0.01)。二分类Logistic回归分析结果显示,患者高脂血症史[OR=3.672,95%CI(1.499,8.992),P=0.004]、右雷佐生使用情况[OR=0.154,95%CI(0.072,0.330),P<0.001]与心脏毒性的发生相关。结论 高脂血症史是HER2阳性乳腺癌患者接受吡柔比星+环磷酰胺序贯紫杉醇+曲妥珠单抗致心脏毒性的独立危险因素,而使用右雷佐生则是保护因素。

OBJECTIVE To analyze the influential factors of cardiotoxicity in patients with positive breast cancer of human epidermal growth factor receptor 2(HER-2)treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021,200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity,the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected,and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients,43 patients suffered from cardiotoxicity with the incidence of 21.5%. The proportion of patients with cardiotoxicity during pirarubicin + cyclophosphamide therapy accounted for 5.5%(11/200),and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5%(41/200);the latter was significantly higher than the former(P<0.01). At the same time,the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin + cyclophosphamide therapy [14%(12%,17%)vs. 7%(3%,10%),P<0.001]. Compared with patients without cardiotoxicity,the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher(P<0.01),while the proportion of patients receiving dexrazoxane was significantly lower(P<0.01). Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR=3.672,95% CI(1.499,8.992),P=0.004] and the use of dextrazoxane [OR=0.154,95% CI(0.072,0.330),P<0.001] were associated with the occurrence of cardiotoxicity.CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel + trastuzumab in HER2 positive breast cancer patients,while the use of dextrazoxane is a protective factor.