DNA损伤修复基因胚系突变乳腺癌新辅助化疗疗效分析  

Efficacy analysis of neoadjuvant chemotherapy regimens for patients with breast cancer carrying germline mutations in DNA damage repair genes

作　　者：刘婧思 陈久安 孙洁[1] 姚璐[1] 张娟[1] 解云涛[1] 徐晔[1] Jingsi Liu;Jiuan Chen;Jie Sun;Lu Yao;Juan Zhang;Yuntao Xie;Ye Xu(Familial&Hereditary Cancer Center,Peking University Cancer Hospital&Institute,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Beijing 100142,China)

机构地区：[1]北京大学肿瘤医院家族遗传性肿瘤中心,恶性肿瘤发病机制及转化研究教育部重点实验室,北京市100142

出　　处：《中国肿瘤临床》2023年第10期497-503,共7页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:82072898,81772824);北京市属医院科研培育计划(编号:PX2021042)资助。

摘　　要：目的:分析携带DNA损伤修复(DNA damage repair,DDR)相关基因突变的乳腺癌患者对基础蒽环类新辅助化疗方案(anthracycline,A)、蒽环联合紫杉类新辅助化疗方案(anthracycline-taxane,A-T)、蒽环联合紫杉和铂类新辅助化疗方案(anthracycline-taxane/carboplatin,A-TP)的疗效反应。方法:2003年10月至2015年5月,105例携带DDR基因胚系突变(非BRCA)的原发性乳腺癌患者在北京大学肿瘤医院分别接受A(n=69)、A-T(n=19)、A-TP(n=17)3种新辅助化疗方案。通过χ2检验或Fisher精确检验比较3组患者的病理完全缓解(pathological complete remission,pCR)率;采用Kaplan-Meier生存分析和Cox回归模型分析患者的乳腺癌特异生存(breast cancer-specific survival,BCSS)及无复发生存(recurrence-free survival,RFS)。结果:93.3%(98/105)的患者接受了4~8个周期的新辅助化疗。接受A、A-T、A-TP新辅助方案的3组患者的pCR率分别为11.6%、21.1%和35.3%。A-TP组pCR率显著高于A组(P=0.028),A-TP组pCR率也高于A-T组,但未达到统计学差异。经过65.6个月的中位随访,A-TP组的BCSS(HR=0.50,95%CI:0.09~2.73,P=0.41)和RFS(HR=0.51,95%CI:0.15~1.74,P=0.27)略优于A-T组,但无统计学差异。结论:DDR基因胚系突变患者应用A-TP新辅助化疗方案可显著提高pCR率,加入铂类药物或可提高患者的药物反应性及预后。Objective:To explore the efficacy of anthracycline(A),anthracycline-taxane(A-T),and anthracycline-taxane/carboplatin(A-TP)neoadjuvant chemotherapy regimens in patients with breast cancer harboring germline mutations in DNA damage repair(DDR)genes.Methods:A total of 105 patients with operable primary breast cancer,carrying germline mutations in any of the 15 DDR genes,were given neoadjuvant treatment in Peking University Cancer Hospital&Institute from October 2003 to May 2015.Among them,69,19,and 17 patients received the neoadjuvant regimens A,A-T,and A-TP,respectively.The pathological complete remission(pCR)rates of the three groups to the neoadjuvant chemotherapy were compared byχ2 or Fisher’s exact test.The Kaplan-Meier survival analysis and Cox proportional hazards model were used to determine the breast cancer-specific survival(BCSS)and recurrence-free survival(RFS)rates in patients with breast cancer.Results:93.3%of patients received four to eight cycles of neoadjuvant chemotherapy.The respective pCR rates of the A,A-T,and A-TP groups were 11.6%,21.1%,and 35.3%.The pCR rate of the A-TP group was significantly higher than that of the A group(P=0.028).The A-TP group also displayed a better pCR rate relative to that of the A-T group,but the difference was not statistically significant.After a median follow-up of 65.6 months,DDR gene mutation carriers treated with the A-TP regimen exhibited better BCSS(hazard ratio[HR]=0.50,95%confidence interval[CI]:0.09–2.73,P=0.41)and RFS(HR=0.51,95%CI:0.15–1.74,P=0.27)than patients treated with the A-T regimen;however,the variation did not reach the significance threshold.Conclusions:Results of this study suggested that patients with germline mutations in DDR genes can achieve higher pCR rates when carboplatin is added to the standard A-T-based neoadjuvant chemotherapy.The A-TP regimen also showed a trend towards better prognosis compared with the A regimen.

关 键 词：乳腺癌 DNA 损伤修复基因 新辅助化疗 病理完全缓解 

分 类 号：R737.9[医药卫生—肿瘤]