Department of Breast Surgery, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Guangzhou, 510080, China.
Foshan Women and Children Hospital, Foshan, China.
BMC Med. 2022 Apr 29;20(1):142. doi: 10.1186/s12916-022-02346-9.
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.
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.
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 = 0.031), but had comparable disease-free survival (p = 0.271).
Our results demonstrate the distinct clinical and molecular features and clinical outcomes of HER2-low breast tumors.
HER2-低乳腺癌与 HER2-零乳腺癌具有不同的临床病理特征；然而，其遗传特征的差异尚不清楚。本研究根据 HER2 状态研究了乳腺癌的临床和分子特征。
我们分析了 523 例中国女性乳腺癌患者的临床病理和基因组数据。使用商业 520 基因面板对乳腺癌样本进行靶向下一代测序（NGS）生成基因组数据。该队列根据免疫组织化学和荧光原位杂交结果的 HER2 状态分为 HER2-零（n = 90）、HER2-低（n = 231）和 HER2-阳性（n = 202）。
HER2-低乳腺癌肿瘤富含激素受体阳性肿瘤，且 Ki67 表达水平较低。不同 HER2 亚组的基因发生了不同的突变。与 HER2-阳性（p < 0.001）和 HER2-零（p < 0.01）乳腺癌相比，HER2-低肿瘤中参与 PI3K-Akt 信号通路的突变明显更多。与 HER2-低乳腺癌相比，HER2-零肿瘤中检查点因子（p < 0.01）、范可尼贫血（p < 0.05）、p53 信号和细胞周期途径（p < 0.05）的突变更多。与 HER2-零肿瘤相比，HER2-低肿瘤新辅助治疗后的病理完全缓解率明显较低（15.9%对 37.5%，p = 0.042），且随访时间点复发/进展患者比例较高（p = 0.031），但无病生存率相当（p = 0.271）。
我们的研究结果表明，HER2-低乳腺癌具有独特的临床和分子特征及临床结局。
