论文部分内容阅读
目的探讨多基因联合检测预测激素受体阳性晚期乳腺癌患者内分泌治疗耐药的临床应用价值。方法采用回顾性病例分析方法,收集2015年1月至2016年8月中国医学科学院北京协和医学院肿瘤医院收治的30例激素受体阳性晚期乳腺癌患者的临床资料。于患者治疗前采集其外周血10 ml,利用目标区域捕获测序技术检测循环肿瘤DNA(ct DNA)突变情况。根据患者是否存在耐药相关基因(TP53、PIK3CA、m TOR、ERBB2、ESR1、FGFR1)突变,将其分为基因突变组和非基因突变组。分析内分泌治疗耐药与基因突变的关系。采用Kaplan-Meier法绘制2组患者的无进展生存(PFS)曲线,用Log-rank检验比较两者之间的差异。并用χ~2检验比较基因突变组与非基因突变组患者发生原发耐药的差异。结果在30例患者中,基因突变组与非基因突变组患者分别有20例和10例。随访1~19个月,中位随访时间为3个月,2组患者中位PFS分别为3个月和5个月,并且,基因突变组患者6个月PFS率明显低于非基因突变组(10%比50%,χ~2=8.328,P=0.004)。20例基因突变组患者中,原发耐药者18例,继发耐药者2例,而10例非基因突变组患者中原发耐药者5例,继发耐药者5例;基因突变组原发耐药者比非基因突变组多(χ~2=5.963,P=0.026)。结论联合检测多个耐药相关基因的ct DNA,能够预测晚期乳腺癌患者内分泌治疗耐药。
Objective To investigate the clinical value of multi-gene combined detection in predicting endocrine resistance in patients with hormone receptor-positive advanced breast cancer. Methods A retrospective case analysis method was used to collect the clinical data of 30 patients with hormone receptor-positive advanced breast cancer who were admitted to the Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Hospital from January 2015 to August 2016. Peripheral blood samples of 10 ml were collected before treatment, and the mutation of circulating tumor DNA (ct DNA) was detected by target region capture sequencing. The patients were divided into gene mutation group and non-gene mutation group according to the presence or absence of resistance-related genes (TP53, PIK3CA, mTOR, ERBB2, ESR1, FGFR1). Analysis of the relationship between endocrine therapy resistance and gene mutation. Kaplan-Meier method was used to draw the progression-free survival (PFS) curves of two groups of patients, Log-rank test was used to compare the differences between the two. And χ ~ 2 test was used to compare the difference of primary drug resistance between gene mutation group and non-gene mutation group. Results Among 30 patients, there were 20 cases and 10 cases of gene mutation group and non-gene mutation group respectively. The follow-up ranged from 1 to 19 months. The median follow-up time was 3 months. The median PFS of the two groups were 3 months and 5 months respectively. Moreover, the 6-month PFS rate of the gene mutation group was significantly lower than that of the non-gene mutation group (10% vs. 50%, χ ~ 2 = 8.328, P = 0.004). Among the 20 patients with mutations, 18 were primary drug resistance and 2 were secondary drug resistance, while 5 were primary drug resistance and 5 were secondary drug resistance in 10 non-gene mutation patients. Genes Mutant group of primary resistance than non-gene mutation group (χ ~ 2 = 5.963, P = 0.026). Conclusion The combined detection of ct DNA in multiple drug resistance related genes can predict the endocrine resistance in patients with advanced breast cancer.