研究动态
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利用机构开发的临床靶向测序来提高乳腺癌患者的生存率:七年经验。

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience.

发表日期:2024 Aug 21
作者: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im
来源: GENES & DEVELOPMENT

摘要:

考虑到亚洲乳腺癌(BC)患者的高疾病负担和独特特征,有必要全面了解该人群的遗传特征。通过韩国研究驱动医院项目开发了机构靶向测序平台,并将其纳入临床实践。本研究探讨了靶向下一代测序 (NGS) 的使用及其在现实世界中晚期/转移性 BC 患者中的结果。我们回顾了使用定制测序平台 - FiRST Cancer Panel 对 BC 患者进行 NGS 测试的结果。 FCP) - 七年多了。我们系统地描述了 FCP 在精确诊断、个性化治疗策略和阐明疾病发病机制方面的临床转化。对 522 名 BC 患者的 548 个样本进行了 NGS 测试。 97.6% 的测试样本至少含有一种致病性改变。常见的改变包括TP53(56.2%)、PIK3CA(31.2%)、GATA3(13.8%)、BRCA2(10.2%)突变,以及CCND1(10.8%)、FGF19(10.0%)和ERBB2(9.5%)扩增)。 ERBB2 扩增的 NGS 分析与 HER2 免疫组织化学和原位杂交密切相关。 RNA 组分析发现了潜在的可操作和预后融合基因。 FCP 有效筛选了潜在的种系致病/可能致病突变。 10.3% 的 BC 患者接受了 NGS 指导下的匹配治疗,带来了显着的总生存优势 (p=0.022),特别是对于转移性 BC。  临床NGS提供了多方面的好处,加深了我们对疾病的了解,提高了诊断精度,并为靶向治疗铺平了道路。 FCP 的具体优势凸显了多基因检测对 BC 的重要性,特别是对于转移性疾病。
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform - FiRST Cancer Panel (FCP) - over seven years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.NGS tests were conducted on 548 samples from 522 patients with BC. 97.6% of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53(56.2%), PIK3CA(31.2%), GATA3(13.8%), BRCA2(10.2%), and amplifications of CCND1(10.8%), FGF19(10.0%), and ERBB2(9.5%). NGS analysis of ERBB2 amplification correlated well with HER2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. 10.3% of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.  .Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.