注射用曲妥珠单抗对人表皮生长因子受体2阳性晚期乳腺癌化疗患者血清肿瘤标志物及免疫功能的影响

Effects of herceptin on the serum tumor markers in patients with HER-2 positive advanced breast cancer treated with chemotherapy and its influence on the immune function

目的 观察注射用曲妥珠单抗对人表皮生长因子受体2（HER-2）阳性晚期乳腺癌患者血清肿瘤标志物及免疫功能的影响.方法 2013年1月至2014年6月我院收治的76例HER-2阳性晚期乳腺癌患者分为观察组38例和对照组38例,同期入组50名健康体检者作为空白组.对照组采用吉西他滨联合卡培他滨化疗方案治疗,吉西他滨1000 mg/m2,第1、8天静脉滴注,卡培他滨2500 mg/m2,第1~14天静脉滴注;观察组在对照组的基础上再给予注射用曲妥珠单抗治疗,首次4 mg/kg,以后2 mg/kg,1次/周.3周为1个周期,治疗4个周期.治疗前后采用流式细胞术检测患者外周血淋巴细胞亚群变化情况,采用酶联免疫法检测癌胚抗原（CEA）、癌相关糖蛋白抗原（CA153）、组织多肽特异性抗原（TPS）.比较两组近期疗效、生存率及不良反应发生率差异.结果 （1）观察组的临床获益率为89.47%（34/38）,对照组为63.15%（24/38）,差异有统计学意义（χ2=8.508,P〈0.05）.观察组1年生存率为65.79%,对照组为39.47%,差异有统计学意义（χ2=5.278,P〈0.05）.观察组2年生存率为42.11%,对照组为21.05%,差异有统计学意义（χ2=3.897,P〈0.05）.（2）观察组和对照组治疗后CD3＋、CD4＋、CD4＋/CD8＋分别为（51.5±5.2）%和（52.7±4.4）%、（24.1±5.6）%和（26.7±5.0）%、（0.81±0.10）和（0.86±0.13）,均较治疗前明显降低（t值分别为5.734、4.824、6.056、5.428、3.602、3.643,P均〈0.05）,观察组和对照组治疗前后淋巴细胞亚群差异无统计学意义（P均〉0.05）,观察组和对照组治疗后CD3＋、CD4＋、CD4＋/CD8＋均明显低于健康空白组（F=14.484、9.371、8.213,P均〈0.01）.（3）观察组和对照组治疗后CEA、CA153、TPS分别为（5.05±2.03） μg/L和（7.25±2.70） μg/L、（36.04±12.05）IU/ml和（55.42±18.23）IU/ml、（262.43±53.38）IU/ml和（355.21±47.80）IU/ml,均较治疗前明显下降（t值分别为8.743、3.805、7.929、5.271、9.512、6.389,P〈0.05）,且观察组明显低于对照组（t=3.353、3.665、3.442,P〈0.05）.（4）观察组疼痛、发热的不良反应发生率分别为34.21%、28.95%,明显高于对照组（0例）,差异有统计学意义（χ2=15.683、12.862, P均〈0.01）.结论 曲妥珠单抗能够协同降低HER-2阳性晚期乳腺癌患者血清肿瘤标志物含量,改善化疗近期疗效,延长生存周期;且未增加免疫功能损伤,但增加疼痛、发热发生率,应及时进行针对性处理,提高化疗依从性.

Objective To explore the effects of herceptin on the serum tumor markers in patients with HER-2 positive advanced breast cancer treated with chemotherapy and its influence on the immune function.Methods Seventy-six patients with HER2-positive advanced breast cancer from January 2013 to June 2014 in Xiangyang No.1 People＆#39;s Hospital Affiliated to Hubei University of Medicine were divided into the observation group （38 cases） and the control group （38 cases）,fifty healthy subjects in the same period were selected as the blank group.The control group received gemcitabine combined with capecitabine,gemcitabine 1000 mg / m2 via intravenous infusion in the first and eighth day,capecitabine 2500 mg/m2 via intravenous drip from the first day to fourteenth day;the observation group were given trastuzumab on the basis of the control group,4 mg/kg for the first time,then 2 mg/kg,1 time/week,three weeks for a course,have been given for four courses.The peripheral blood lymphocyte subsets were detected by flow cytometry,the Carcinoembryonic antigen （CEA）,cancer-associated glycoprotein antigen （CA153） and tissue polypeptide specific antigen （TPS） were detected by enzyme-linked immunoassay.The short-term efficacy,survival and adverse reactions incidence rate in the two groups were compared.Results （1） The clinical benefit rate of the observation group was higher than that of the control group （89.47% vs.63.15%,χ2=8.508,P〈0.05）,the 1-year survival rate of the observation group was 65.79%,the control group was 39.47%,the difference was statistically significant （χ2=5.278,P〈0.05）,the 2-year survival rate of the observation group was 42.11%,the control group was 21.05%,the difference was statistically significant （χ2=3.897,P〈0.05）.（2） The CD3＋,CD4＋ and CD4＋/CD8＋ of the observation group and the control group after treatment were （51.5±5.2）%,（52.7±4.4）%,（24.1±5.6）%,（26.7±5.0）%,（0.81±0.10）,（0.86±0.13）,respectively,which were lower than those collected before treatment （t=5.734,4.824,6.056,5.428,3.602,3.643,P〈0.05））,there were no significant differences in lymphocyte subset between the observation group and the control group before and after treatment （P〉0.05）,the CD3＋,CD4＋,CD4＋/CD8＋ of the observation group and the control group after treatment were significantly lower than those of the blank group （F=14.484,9.371,8.213,P〈0.01）.（3） The CEA,CA153 and TPS of the observation group and the control group after treatment were （5.05±2.03） μg/L,（7.25±2.70）μg/L,（36.04±12.05） IU/ml,（55.42±18.23） IU/ml,（262.43±53.38） IU/ml,（355.21±47.80） IU/ml,which were significantly lower than those before treatment （t=8.743,3.805,7.929,5.271,9.512,6.389,P〈0.05）,the observation group was significantly lower than the control group （t=3.353、3.665、3.442,P〈0.05）.（4） The incidence rate of pain and fever in the observation group were 34.21% and 28.95%,respectively,which were significantly higher than those in the control group,the difference was statistically significant （χ2=15.683,12.862,P〈0.01）.Conclusion Trastuzumab can synergistically reduce the serum tumor marker content in the treatment of patients with HER 2-positive advanced breast cancer,effectively improve the short-term efficacy of conventional chemotherapy,extend the life span,without the cause of significant damage to the immune function,but it can significantly increase the incidence rate of pain and fever,so it is necessary to carry out targeted method to improve chemotherapy compliance.