HR+/HER2−乳腺癌高复发风险与 DNA修复异常有关——基于METABRIC数据库分析
High Recurrence Risk in HR+/HER2− Breast Cancer Is Associated with DNA Repair Defects—An Analysis Based on the METABRIC Database
DOI: 10.12677/acm.2026.1631100, PDF,    科研立项经费支持
作者: 黄 永, 魏一睿, 李朝阳, 李一凤, 程 巧*：重庆医科大学附属第一医院，乳腺甲状腺外科，重庆
关键词: 乳腺癌；HR+/HER2−；遗传特征；DNA修复；精准肿瘤学；Breast Cancer； HR+/HER2−； Genetic Characteristics； DNA Repair； Precision Oncology
摘要: 目的：乳腺癌是全球最常见的恶性肿瘤之一，其中激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2−)亚型通常预后较好。然而，约5%~10%的HR+/HER2−患者在2.5年内发生转移，这凸显了优化风险分层和实施靶向干预的迫切性。本研究旨在鉴定该高危亚群的遗传特征并探索潜在的治疗靶点。方法：利用METABRIC数据库数据，根据临床预后将患者分为“高危”和“低危”两组。通过多组学差异分析，系统表征高危患者的分子图谱。利用TCGA乳腺癌队列对研究结果的稳健性进行外部验证。结果：多组学分析揭示了高危HR+/HER2−乳腺癌患者独特的分子特征。通路富集分析显示关键生物学过程显著受损，特别是DNA双链断裂修复机制。外部验证显示，较高的同源重组缺陷(HRD)评分与较差的无进展生存期相关。结论：这些发现加深了对高危HR+/HER2−乳腺癌遗传和分子驱动因素的理解，并为开发靶向治疗策略提供了关键见解，有助于推动精准肿瘤学的发展。
Abstract: Objective: Breast cancer remains one of the most prevalent malignancies worldwide, with the hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) subtype generally associated with favorable outcomes. However, approximately 5%~10% of HR+/HER2− patients develop metastases within 2.5 years, highlighting the need for improved risk stratification and targeted interventions. This study aims to identify the genetic characteristics of this high-risk subgroup and explore potential therapeutic targets. Methods: Using data from the METABRIC database, patients were classified into distinct “high-risk” and “low-risk” categories based on clinical outcomes. Multi-omics differential analysis was performed to systematically characterize the molecular landscape of high-risk patients. The robustness of the findings was externally validated using the TCGA breast cancer cohort. Results: Multi-omics analysis revealed distinct molecular features in high-risk HR+/HER2− breast cancer patients. Pathway enrichment analysis demonstrated significant impairments in key biological processes, particularly in DNA double-strand break repair mechanisms. In external validation, higher homologous recombination deficiency (HRD) scores were associated with poorer progression-free survival. Conclusion: These findings enhance the understanding of the genetic and molecular drivers of high-risk HR+/HER2− breast cancer and provide critical insights for developing targeted therapeutic strategies, contributing to advances in precision oncology.
文章引用：黄永, 魏一睿, 李朝阳, 李一凤, 程巧. HR+/HER2−乳腺癌高复发风险与 DNA修复异常有关——基于METABRIC数据库分析[J]. 临床医学进展, 2026, 16(3): 2964-2978. https://doi.org/10.12677/acm.2026.1631100

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