Liquid biopsy, a minimally invasive approach for detecting tumor biomarkers in blood, has emerged as a leading-edge technique in cancer precision medicine. New evidence has shown that liquid biopsies can incidentally detect pathogenic germline variants (PGVs) associated with cancer predisposition, including in patients with a cancer for which genetic testing is not recommended. The ability to detect these incidental PGV in cancer patients through liquid biopsy raises important questions regarding the management of this information and its clinical implications. This incidental identification of PGVs raises concerns about cancer predisposition and the potential impact on patient management, not only in terms of providing access to treatment based on the tumor molecular profiling, but also the management of revealing genetic predisposition in patients and families. Understanding how to interpret this information is essential to ensure proper decision-making and to optimize cancer treatment and prevention strategies. In this review we provide a comprehensive summary of current evidence of incidental PGVs in cancer predisposition genes identified by liquid biopsy in patients with cancer. We critically review the methodological considerations of liquid biopsy as a tool for germline diagnosis, clinical utility and potential implications for cancer prevention, treatment, and research.

液体活检是一种检测血液中肿瘤生物标志物的微创方法，已成为癌症精准医学的前沿技术。新证据表明，液体活检可以偶然检测到与癌症易感性相关的致病性种系变异（PGV），包括不建议进行基因检测的癌症患者。通过液体活检检测癌症患者中这些偶然的 PGV 的能力提出了有关该信息的管理及其临床意义的重要问题。 PGV 的偶然鉴定引起了人们对癌症易感性及其对患者管理的潜在影响的担忧，不仅在提供基于肿瘤分子分析的治疗机会方面，而且在揭示患者和家庭遗传易感性的管理方面。了解如何解释这些信息对于确保正确决策并优化癌症治疗和预防策略至关重要。在这篇综述中，我们全面总结了癌症患者液体活检发现的癌症易感基因中附带 PGV 的当前证据。我们批判性地回顾了液体活检作为种系诊断工具的方法学考虑、临床实用性以及对癌症预防、治疗和研究的潜在影响。