Kou Furong, Liu Huimin, Zhang Yaxin, Liao Xingyu, Hu Li, Sun Jie, Zhang Juan, Xu Ye, Yao Lu, Xie Yuntao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Comprehensive Clinical Trial Ward, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Beijing, China.
JCO Precis Oncol. 2025 Mar;9:e2400679. doi: 10.1200/PO-24-00679. Epub 2025 Mar 26.
Data about the clinical impact of human epidermal growth factor receptor 2 (HER2)-low expression in -mutated breast cancer (BC) are limited. This study aimed to clarify the clinical relevance of HER2-low in operable -mutated BC.
A total of 495 HER2-negative operable BC with germline pathogenic variants treated at our institute between October 2003 and September 2020 were included. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+/fluorescence in situ hybridization-negative, while HER2-zero as IHC 0. Tumor DNA from 25 -mutated triple-negative BCs (TNBCs) was subjected to whole-exome sequencing.
Among the 186 carriers, 38.8% of TNBC (n = 121) and 52.3% of hormone receptor-positive/HER2-negative BC (n = 65) exhibited HER2-low tumors in the subgroup; among 309 carriers, 44.9% of TNBC (n = 49) and 68.1% of hormone receptor-positive/HER2-negative BC (n = 260) exhibited HER2-low tumors in the subgroup. After a median follow-up of 10.9 years (range, 1.23-19.8 years), among -mutated TNBC, HER2-low tumors were significantly associated with better recurrence-free survival (RFS; 10-year RFS: 90.3% 75.1%; = .015), distant recurrence-free survival (DRFS; 10-year DRFS: 92.4% 76.5%; = .010), and overall survival (OS; 10-year OS: 94.6% 77.4%; = .007) than HER2-zero tumors. However, the impact of HER2-low in survival was not observed either in -mutated TNBC or in and -mutated hormone receptor-positive/HER2-negative BC. Notably, mutated TNBC with HER2-low tumors showed higher homologous recombination deficiency scores than those with HER2-zero tumors.
-mutated TNBC patients with HER2-low tumors have a significantly favorable survival, highlighting the possibility of stratifying these patients into two subgroups on the basis of HER2-low status.
关于人表皮生长因子受体2（HER2）低表达在突变型乳腺癌（BC）中的临床影响的数据有限。本研究旨在阐明HER2低表达在可手术突变型BC中的临床相关性。
纳入2003年10月至2020年9月在我院接受治疗的495例携带种系致病变异的HER2阴性可手术BC患者。HER2低表达定义为免疫组织化学（IHC）1+或2+/荧光原位杂交阴性，而HER2零表达定义为IHC 0。对25例突变型三阴性乳腺癌（TNBC）的肿瘤DNA进行全外显子测序。
在186例携带者中，该亚组中44.9%的TNBC（n = 49）和68.1%的激素受体阳性/HER2阴性BC（n = 260）表现为HER2低表达肿瘤；在309例携带者中，该亚组中44.9%的TNBC（n = 49）和68.1%的激素受体阳性/HER2阴性BC（n = 260）表现为HER2低表达肿瘤。中位随访10.9年（范围1.23 - 19.8年）后，在突变型TNBC中，HER2低表达肿瘤与HER2零表达肿瘤相比，无复发生存期（RFS；10年RFS：90.3%对75.1%；P = 0.015）、远处无复发生存期（DRFS；10年DRFS：92.4%对76.5%；P = 0.010）和总生存期（OS；10年OS：94.6%对77.
