At least 5% of cancer diagnoses are attributed to a causal pathogenic or likely pathogenic germline genetic variant (hereditary cancer syndrome—HCS). These individuals are burdened with lifelong surveillance monitoring organs for a wide spectrum of cancers. This is associated with substantial uncertainty and anxiety in the time between screening tests and while the individuals are awaiting results. Cell-free DNA (cfDNA) sequencing has recently shown potential as a non-invasive strategy for monitoring cancer. There is an opportunity for high-yield cancer early detection in HCS. To assess clinical validity of cfDNA in individuals with HCS, representatives from eight genetics centers from across Canada founded the CHARM (cfDNA in Hereditary and High-Risk Malignancies) Consortium in 2017. In this perspective, we discuss operationalization of this consortium and early data emerging from the most common and well-characterized HCSs: hereditary breast and ovarian cancer, Lynch syndrome, Li-Fraumeni syndrome, and Neurofibromatosis type 1. We identify opportunities for the incorporation of cfDNA sequencing into surveillance protocols; these opportunities are backed by examples of earlier cancer detection efficacy in HCSs from the CHARM Consortium. We seek to establish a paradigm shift in early cancer surveillance in individuals with HCSs, away from highly centralized, regimented medical screening visits and toward more accessible, frequent, and proactive care for these high-risk individuals.

至少 5% 的癌症诊断归因于致病性或可能致病性种系遗传变异（遗传性癌症综合征 - HCS）。这些人背负着对多种癌症进行终生监测的监测器官。这与筛查测试之间和个人等待结果期间的巨大不确定性和焦虑有关。游离 DNA (cfDNA) 测序最近显示出作为监测癌症的非侵入性策略的潜力。HCS 有机会进行高产癌症早期检测。为了评估 cfDNA 在 HCS 患者中的临床有效性，来自加拿大各地八个遗传学中心的代表于 2017 年成立了 CHARM（遗传性​​和高风险恶性肿瘤中的 cfDNA）联盟。从这个角度来看，我们讨论该联盟的运作和早期数据的出现来自最常见且特征明确的 HCS：遗传性乳腺癌和卵巢癌、Lynch 综合征、Li-Fraumeni 综合征和 1 型神经纤维瘤病。我们确定了将 cfDNA 测序纳入监测方案的机会；这些机会得到了来自 CHARM 联盟的 HCS 早期癌症检测功效实例的支持。我们寻求在 HCS 个体的早期癌症监测方面建立范式转变，从高度集中、严格的医疗筛查就诊转向对这些高危个体进行更容易、更频繁和更主动的护理。