Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low

作者：Xie Hu, Ping Yang, Songhao Chen, Gang Wei, Lijuan Yuan, Zhenyu Yang, Li Gong, Li He, Lin Yang, Shujia Peng, Yanming Dong, Xianli He, Guo‐Qiang Bao · 发表于：Breast Cancer Research · 年份：2023 · DOI：10.1186/s13058-023-01639-y · 被引用次数：57 · 研究领域：Cancer Cells and Metastasis、Cancer Immunotherapy and Biomarkers、Single-cell and spatial transcriptomics

Abstract Background HER2-low could be found in some patients with triple-negative breast cancer (TNBC). However, its potential impacts on clinical features and tumor biological characteristics in TNBC remain unclear. Methods We enrolled 251 consecutive TNBC patients retrospectively, including 157 HER2-low (HER2 low ) and 94 HER2-negtive (HER2 neg ) patients to investigate the clinical and prognostic features. Then, we performed single-cell RNA sequencing (scRNA-seq) with another seven TNBC samples (HER2 neg vs. HER2 low , 4 vs. 3) prospectively to further explore the differences of tumor biological properties between the two TNBC phenotypes. The underlying molecular distinctions were also explored and then verified in the additional TNBC samples. Results Compared with HER2 neg TNBC, HER2 low TNBC patients exhibited malignant clinical features with larger tumor size ( P = 0.04), more lymph nodes involvement ( P = 0.02), higher histological grade of lesions ( P < 0.001), higher Ki67 status ( P < 0.01), and a worse prognosis ( P < 0.001; HR [CI 95%] = 3.44 [2.10–5.62]). Cox proportional hazards analysis showed that neoadjuvant systemic therapy, lymph nodes involvement and Ki67 levels were prognostic factors in HER2 low TNBC but not in HER2 neg TNBC patients. ScRNA-seq revealed that HER2 low TNBC which showed more metabolically active and aggressive hallmarks, while HER2 neg TNBC exhibited signatures more involved in immune activities with higher expressions of immunoglo...