Genomic landscape of circulating tumor DNA in HER2-low metastatic breast cancer  

作　　者：Zongbi Yi Kaixiang Feng Dan Lv Yanfang Guan Youcheng Shao Fei Ma Binghe Xu 

机构地区：[1]Department of Radiation and Medical Oncology,Hubei Key Laboratory of Tumor Biological Behaviors,Hubei Cancer Clinical Study Center,Zhongnan Hospital of Wuhan University,Wuhan,China [2]Department of Breast and Thyroid Surgery,Hubei Key Laboratory of Tumor Biological Behaviors,Hubei Cancer Clinical Study Center,Zhongnan Hospital of Wuhan University,Wuhan,China [3]Department of Medical Oncology,Cancer Hospital of China Medical University,Liaoning Cancer Hospital,Shenyang,China [4]Geneplus-Beijing,Beijing,China [5]Department of Pathology and Pathophysiology,TaiKang Medical School(School of Basic Medical Sciences),Wuhan University,Wuhan,China [6]Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2025年第1期293-302,共10页信号转导与靶向治疗(英文)

基　　金：supported by the National Science Fund of China(Grant No.82303823);the CAMS Innovation Fund for Medical Sciences(Grant Nos.2021-I2M-1-014,2023-12M-2-004);the Wuhan Municipal Science and Technology Bureau Knowledge Innovation Special Project“Dawn Plan”Project(Grant No.KYXM2022011);the Youth Interdisciplinary Special Fund of Zhongnan Hospital of Wuhan University(Grant No.ZNQNJC2022006).

摘　　要：The large population of HER2-low breast cancer patients necessitates further research to provide enhanced clinical guidance.In this study,we retrospectively analyzed 1071 metastatic breast cancer(MBC)patients and the circulating tumor DNA(ctDNA)to investigate clinicopathological and genetic alterations of HER2-low MBC patients.The effect of HER2-low status on different treatment modalities was explored in two prospective clinical trials(NCT03412383,NCT01917279)and a retrospective study.Ourfindings suggest TP53,PIK3CA,and ESR1 are frequently mutated genes in HER2-low MBC.Compared to the HER2-0 group,mutations observed in the HER2-low group are more closely associated with metabolic pathway alterations.Additionally,among patients with ERBB2 mutations and treated with pyrotinib,the HER2-low group may experience superior prognosis when compared to the HER2-0 group.Notably,we did notfind any statistically significant disparity in the response to chemotherapy,endocrine therapy,or CDK4/6 inhibitor therapy between HER2-0 and HER2-low breast cancer patients.Interestingly,within the subgroup of individuals with metabolic pathway-related gene mutations,we found that HER2-low group exhibited a more favorable response to these treatments compared to HER2-0 group.Additionally,dynamic analysis showed the HER2-low MBC patients whose molecular tumor burden index decreased or achieved early clearance of ctDNA after the initial two treatment cycles,exhibited prolonged survival.Moreover,we classified HER2-low MBC into three clusters,providing a reference for subsequent treatment with enhanced precision.Our study offers valuable insights into the biology of HER2-low MBC and may provide reference for personalized treatment strategies.

关 键 词：alterations HER2 TREATMENT 

分 类 号：R73[医药卫生—肿瘤]