• 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, and Ning Liao.
• Department of Breast Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China.
• Bmc Med. 2022 Apr 29; 20 (1): 142.

BackgroundHER2-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.MethodsWe 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.ResultsHER2-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 = 0.031), but had comparable disease-free survival (p = 0.271).ConclusionOur results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.© 2022. The Author(s).

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