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Cancer Lett ; 588: 216763, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38403109

RESUMO

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Mutação em Linhagem Germinativa , Fosfatidilinositol 3-Quinases/genética , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Mutação , China
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