ctDNA基因突变状态与激素受体阳性乳腺癌氟维司群疗效的关系  

Relationship Research between ctDNAGene Mutation Status and Effect of Fulvestrant for Hormone Receptor Positive Breast Cancer

作　　者：刘华文 张瑶 邓超 谭建军 LIU Huawen;ZHANG Yao;DENG Chao;TAN Jianjun(Department of Oncology,Chongqing University Affiliated Three Gorges Hospital,Chongqing 404100)

机构地区：[1]重庆大学附属三峡医院肿瘤科,重庆404100

出　　处：《智慧健康》2024年第28期42-45,共4页Smart Healthcare

基　　金：重庆市科卫联合医学科研项目《循环肿瘤DNA监测在ER阳性乳腺癌患者氟维司群内分泌治疗管理中的价值》(项目编号:2021MSXM271)。

摘　　要：目的探讨循环肿瘤DNA(ctDNA)中9种基因突变状态与氟维司群治疗激素受体(HR)阳性乳腺癌效果的关系。方法纳入61例经病理学确诊为HR阳性且人类表皮生长因子受体2(Her2)未扩增的乳腺癌患者,进行肿瘤组织测序,并收集氟维司群治疗前、治疗后3个月的血浆进行ctDNA测序。评价氟维司群治疗3个月后和6个月后患者的有效率。利用logistic回归分析治疗前ctDNA中9基因突变状态突变与治疗3个月以及治疗3个月与6个月后疗效的相关性。结果初步分析发现ESR1、TP53、PIK3CA、ERBB2、MTOR、KRAS、RB1、AKT1、TSC2在肿瘤组织与ctDNA中的突变符合率分别为88.2%、76.5%、84.2%、83.3%、71.4%、80.0%、62.5%、71.4%和80.0%。61例患者治疗前ctDNA中检测出ESR1、TP53、PIK3CA、ERBB2、MTOR、KRAS、RB1、AKT1、TSC2的突变分别为24.6%,21.3%,26.2%,16.4%,16.4%,19.7%,8.2%,8.2%,6.6%。分别利用RECIST v1.1标准评价了氟维司群治疗3个月后和6个月后患者的有效率,分别为19.7%和23%。单因素Logistic回归分析发现治疗前ctDNA中9种基因的突变并非影响患者治疗3个月后有效的因素。而治疗后3个月ctDNA中TSC2的突变与患者治疗6个月后疗效密切相关(P=0.039)。结论ctDNA中TSC2的突变可能与HR阳性乳腺癌氟维司群疗效相关,需要进行更多治疗时间点的监测及多中心病例的验证。Objective To investigate the relationship between mutation status of 9 genes in circulating tumor DNA(ctDNA)and effect of fulvestrant in treatment of hormone receptor(HR)positive breast cancer.Methods The paper included 61 patients with HR positive breast cancer with no hyperplasia of human epidermal growth factor receptor 2(Her2)based on pathological diagnosis.Tumor tissue sequencing was carried out,and plasma samples before and 3 months after fulvestrant treatment were collected for ctDNA sequencing.Effective rate of fulvestrant treatment after 3 and 6 months was evaluated.Correlation between mutation status of 9 genes in ctDNA before treatment and effect after 3 months of treatment,as well as after 3 and 6 months of treatment was investigated with logistic regression analysis.Results Preliminary analysis revealed,mutation coincidence rates of ESR1,TP53,PIK3CA,ERBB2,MTOR,KRAS,RB1,AKT1,and TSC2 in tumor tissues and ctDNA were 88.2%,76.5%,84.2%,83.3%,71.4%,80.0%,62.5%,71.4%,and 80.0%respectively.Mutation rates in ESR1,TP53,PIK3CA,ERBB2,MTOR,KRAS,RB1,AKT1,and TSC2 were detected in ctDNA of 61 cases before treatment were 24.6%,21.3%,26.2%,16.4%,16.4%,19.7%,8.2%,8.2%,and 6.6%respectively.The response rates of patients with fulvestrant treatment after 3 months and 6 months were evaluated with the RECIST v1.1 standard,which were 19.7%and 23%respectively.Univariate logistic regression analysis found,mutations in 9 genes in ctDNA before treatment were not factors affecting effect after 3 months of treatment.The mutation of TSC2 in ctDNA at 3 months after treatment was closely related to effect of those after 6 months of treatment(P=0.039).Conclusion The mutation of TSC2 in ctDNA may be related to effect of fulvestrant of HR positive breast cancer,and more monitoring of treatment time points and verification of multi center cases is needed.

关 键 词：CTDNA 雌激素受体 乳腺癌 氟维司群 突变 

分 类 号：R737.9[医药卫生—肿瘤]