文章：

实体肿瘤患者中同源重组修复突变的发生率及其与临床结局的关联：基于AACR项目GENIE数据集的研究

Prevalence of Homologous Recombination Repair Mutations and Association with Clinical Outcomes in Patients with Solid Tumors: A Study Using the AACR Project GENIE Dataset

原文发布日期：8 February 2025

DOI: 10.3390/cancers17040577

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Mutations inBRCA1and/orBRCA2(BRCAm) and other homologous recombination repair genes (HRRm) are associated with several cancers. We evaluated the prevalence and association with overall survival (OS) of somatic BRCAm and HRRm among patients with advanced solid tumors. Methods: We used deidentified data from the AACR GENIE Biopharma Collaborative dataset derived from patients with tumors genotyped using next-generation sequencing between 1 January 2014 and 31 December 2017. Eligible patients were aged ≥18 years diagnosed with non-small-cell lung, colorectal, breast, bladder, prostate, or pancreatic cancer, with documented BRCA/HRR somatic mutation status. The primary analysis was OS (censored at the start of poly[ADP ribose] polymerase inhibitors [PARPi]/immunotherapy) after initiation of second-line therapy since most patients had sequencing after first-line therapy. Results: Among eligible patients, 242/7022 (3.4%) had BRCAm and 477/5474 (8.7%) had HRRm. Adjusted OS HRs (95% CI) for the primary analysis (using the initiation of second-line therapy as index date) were 0.79 (0.61–1.03) with/without BRCAm (n = 116/n = 3394) and 0.83 (0.69–0.99) with/without HRRm (n = 247/n = 2656); in sensitivity analysis of patients with stage IV disease, HRs were 0.97 (0.68–1.38) with/without BRCAm (n = 58/n = 1847) and 0.92 (0.73–1.18) with/without HRRm (n = 132/n = 1488). Conclusions: Overall, BRCAm and HRRm did not show a strong association with OS, with a trend toward longer OS among patients receiving standard second-line therapies excluding PARPi/immunotherapy.

摘要翻译： 

背景/目的：BRCA1和/或BRCA2（BRCAm）及其他同源重组修复基因（HRRm）的突变与多种癌症相关。本研究评估了晚期实体瘤患者中体细胞BRCAm与HRRm的流行率及其与总生存期（OS）的关联。方法：我们使用来自AACR GENIE生物制药合作数据集的去标识化数据，该数据集来源于2014年1月1日至2017年12月31日期间通过新一代测序进行肿瘤基因分型的患者。符合条件患者为年龄≥18岁、诊断为非小细胞肺癌、结直肠癌、乳腺癌、膀胱癌、前列腺癌或胰腺癌，且具有BRCA/HRR体细胞突变状态记录的患者。主要分析为自二线治疗开始后的OS（以聚[ADP核糖]聚合酶抑制剂[PARPi]/免疫治疗开始为截尾点），因多数患者在一线治疗后进行测序。结果：在符合条件的患者中，242/7022例（3.4%）存在BRCAm，477/5474例（8.7%）存在HRRm。主要分析（以二线治疗开始为索引日期）的校正后OS风险比（95%置信区间）为：存在/不存在BRCAm组0.79（0.61–1.03）（n=116/3394），存在/不存在HRRm组0.83（0.69–0.99）（n=247/2656）；在IV期患者的敏感性分析中，存在/不存在BRCAm组风险比为0.97（0.68–1.38）（n=58/1847），存在/不存在HRRm组为0.92（0.73–1.18）（n=132/1488）。结论：总体而言，BRCAm与HRRm未显示与OS存在强相关性，但在接受标准二线治疗（排除PARPi/免疫治疗）的患者中观察到OS延长的趋势。

原文链接：

Prevalence of Homologous Recombination Repair Mutations and Association with Clinical Outcomes in Patients with Solid Tumors: A Study Using the AACR Project GENIE Dataset