雄激素受体作为三阴性乳腺癌放疗抵抗的介质和生物标志物的临床研究

Clinical study of androgen receptor as a mediator and biomarker of radiotherapy resistance in treatment of triple-negative breast cancer

目的探讨雄激素受体(androgen receptor,AR)作为三阴性乳腺癌放疗抵抗的介质和生物标志物的临床研究。方法选取2016年1月至2018年12月就诊80例三阴性乳腺癌患者,均接受早期乳腺癌治疗手术。术后根据实际情况,患者进行放射和非放射辅助治疗,并分为非放疗组(n=18)和放疗组(n=62)。统计患者一般资料(年龄,身高体重,肿瘤大小、家族肿瘤得病史),并在定期门诊处得到所有患者的复查结果(2年内),计算复发率和生存率。免疫组织化学分析检测AR表达阳性率。多因素Logistic回归分析三阴性乳腺癌患者复发率。结果2组患者年龄、BMI、肿瘤大小、饮酒及吸烟和肿瘤家族史一般资料比较差异无统计学意义(P>0.05)。放疗组较非放疗组肿瘤中的AR表达阳性率升高(P<0.05)。与非放疗组(20.00%,15.38%)相比,放疗组AR高表达复发率(31.25%)增加,AR低表达复发率(13.33%)降低(P<0.05)。与非放疗组(80.00%,84.62%)相比,放疗组AR高表达生存率(71.88%)降低,AR低表达生存率(93.33%)增加(P<0.05)。组织学分级、淋巴结状态和AR状态与之相关(P<0.05),BMI越高、居住地条件越差以及文化程度越低,皮损严重程度越高,而年龄、肿瘤大小和肿瘤家族史与复发情况差异无统计学意义(P>0.05)。结论AR可作为三阴性乳腺癌放疗抵抗的介质和生物标志物,放疗降低AR表达可以提高患者的生存率,降低复发率。

Objective To investigate the effects of androgen receptor(AR)as a mediator and biomarker of radiotherapy resistance in treatment of triple-negative breast cancer.Methods Eighty patients with triple-negative breast cancer who were treated by surgery in our hospital from January 2016 to December 2018 were enrolled in the study,who were divided into radiotherapy group(n=18)and non-radiotherapy group(n=62).The general information(age,height and weight,tumor size,family tumor history),and re-examination results(within two years),relapse rate and survival rate were statisticallt analyzed.Moreover the positive rate of AR expression was detected by immunohistochemistry,and Multivariate Logistic regression analysis was perfomed to analyze the recurrence rate of patients.Results There were no significant differences in general information including age,BMI,tumor size,drinking and smoking,and tumor family history between the two groups(P>0.05).The positive rate of AR in radiotherapy group was 51.61%,which was significantly higher than that(27.78%)in non-radiotherapy group(P<0.05).Moreover the relapse rate(31.25%)in radiotherapy group with high AR expression was significantly higher than that(20.00%)in non-radiotherapy group with high AR expression,moreover,which in radiotherapy group with low AR expression was significantly lower than that in non-radiotherapy group with low AR expression(15.38%vs 13.33%,P<0.05).Compared with those(80.00%,84.62%)in non-radiotherapy group,the survival rate(71.88%)in radiotherapy group with high AR expression was decreased,and the AR low expression survival rate(93.33%)was significantly increased(P<0.05),which was reallted with histological grade,lymph node status and AR status(P<0.05).The higher the BMI,the worse the living conditions,and the lower the education level,the higher the severity of the skin lesions.However there were no significant differences in patient’s age,tumor size,family history anf relapse rate between the two groups(P>0.05).Conclusion AR can be regarded as a mediator and biomarker of radiotherapy resistance in patients with triple-negative breast cancer.The reduction of AR expression by radiotherapy can improve the survival rate of patients and reduce the recurrence rate.