國家衛生研究院 NHRI:Item 3990099045/15909
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    題名: Comprehensive genomic profiling and therapeutic implications for Taiwanese patients with treatment-naïve breast cancer
    作者: Chen, SH;Tse, KP;Lu, YJ;Chen, SJ;Tian, YF;Tan, KT;Li, CF
    貢獻者: National Institute of Cancer Research
    摘要: BackgroundBreast cancer is a heterogeneous disease categorized based on molecular characteristics, including hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression levels. The emergence of profiling technology has revealed multiple driver genomic alterations within each breast cancer subtype, serving as biomarkers to predict treatment outcomes. This study aimed to explore the genomic landscape of breast cancer in the Taiwanese population through comprehensive genomic profiling (CGP) and identify diagnostic and predictive biomarkers.MethodsTargeted next-generation sequencing-based CGP was performed on 116 archived Taiwanese breast cancer specimens, assessing genomic alterations (GAs), including single nucleotide variants, copy number variants, fusion genes, tumor mutation burden (TMB), and microsatellite instability (MSI) status. Predictive variants for FDA-approved therapies were evaluated within each subtype.ResultsIn the cohort, frequent mutations included PIK3CA (39.7%), TP53 (36.2%), KMT2C (9.5%), GATA3 (8.6%), and SF3B1 (6.9%). All subtypes had low TMB, with no MSI-H tumors. Among HR + HER2- patients, 42% (27/65) harbored activating PIK3CA mutations, implying potential sensitivity to PI3K inhibitors and resistance to endocrine therapies. HR + HER2- patients exhibited intrinsic hormonal resistance via FGFR1 gene gain/amplification (15%), exclusive of PI3K/AKT pathway alterations. Aberrations in the PI3K/AKT/mTOR and FGFR pathways were implicated in chemoresistance, with a 52.9% involvement in triple-negative breast cancer. In HER2+ tumors, 50% harbored GAs potentially conferring resistance to anti-HER2 therapies, including PIK3CA mutations (32%), MAP3K1 (2.9%), NF1 (2.9%), and copy number gain/amplification of FGFR1 (18%), FGFR3 (2.9%), EGFR (2.9%), and AKT2 (2.9%).ConclusionThis study presents CGP findings for treatment-na & iuml;ve Taiwanese breast cancer, emphasizing its value in routine breast cancer management, disease classification, and treatment selection. This study offered the comprehensive genomic profiling (CGP) of treatment-na & iuml;ve breast cancer in the Taiwanese population. It underscored the advantages of integrating CGP data into routine breast cancer management, providing valuable insights into disease classification and treatment selection.image
    日期: 2024-06-19
    關聯: Cancer Medicine. 2024 Jun 19;13(12).
    Link to: http://dx.doi.org/10.1002/cam4.7384
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2045-7634&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001249662200001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85196311610
    顯示於類別:[陳尚鴻] 期刊論文

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