Distinct clinical and somatic mutational features of breast tumors with high-, low-, or non-expressing human epidermal growth factor receptor 2 status

作者：Guochun Zhang, Chongyang Ren, Cheukfai Li, Yulei Wang, Bo Chen, Lingzhu Wen, Minghan Jia, Kai Li, Hsiaopei Mok, Li Cao, Xiaoqing Chen, Jiali Lin, Guangnan Wei, Yingzhi Li, Yuchen Zhang, Charles M. Balch, Ning Liao · 发表于：BMC Medicine · 年份：2022 · DOI：10.1186/s12916-022-02346-9 · 被引用次数：148 · 研究领域：Breast Cancer Treatment Studies、HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies

BACKGROUND: HER2-low breast cancers were reported to have distinct clinicopathological characteristics from HER2-zero; however, the difference in their genetic features remains unclear. This study investigated the clinical and molecular features of breast tumors according to HER2 status. METHODS: We analyzed the clinicopathological and genomic data of 523 Chinese women with breast cancer. Genomic data was generated by targeted next-generation sequencing (NGS) of breast tumor samples using a commercial 520 gene panel. The cohort was stratified according to HER2 status as HER2-zero (n = 90), HER2-low (n = 231), and HER2-positive (n = 202) according to their immunohistochemistry and fluorescence in situ hybridization results. RESULTS: HER2-low breast tumors were enriched with hormone receptor-positive tumors, and who had lower Ki67 expression levels. Genes were differentially mutated across HER2 subgroups. HER2-low tumors had significantly more mutations involved in PI3K-Akt signaling than HER2-positive (p < 0.001) and HER2-zero breast tumors (p < 0.01). HER2-zero tumors had more mutations in checkpoint factors (p < 0.01), Fanconi anemia (p < 0.05), and p53 signaling and cell cycle pathway (p < 0.05) compared to HER2-low breast tumors. Compared with HER2-zero tumors, HER2-low tumors had significantly lower pathological complete response rates after neoadjuvant therapy (15.9% vs. 37.5%, p = 0.042) and proportion of relapsed/progressed patients across follow-up time points (p = 0....