The progress that has been made in recent years in relation to liquid biopsies in general and circulating tumor DNA (ctDNA) in particular can be seen as groundbreaking for the future of breast cancer treatment, monitoring and early detection. Cell-free DNA (cfDNA) consists of circulating DNA fragments released by various cell types into the bloodstream. A portion of this cfDNA, known as ctDNA, originates from malignant cells and carries specific genetic mutations. Analysis of ctDNA provides a minimally invasive method for diagnosis, monitoring response to therapy, and detecting the emergence of resistance. Several methods are available for the analysis of ctDNA, each with distinct advantages and limitations. Quantitative polymerase chain reaction is a well-established technique widely used due to its high sensitivity and specificity, particularly for detecting known mutations. In addition to the detection of individual mutations, multigene analyses were developed that could detect several mutations at once, including rarer mutations. These methods are complementary and can be used strategically depending on the clinical question. In the context of metastatic breast cancer, ctDNA holds particular promise as it allows for the dynamic monitoring of tumor evolution. Through ctDNA analysis, mutations in theESR1orPIK3CAgenes, which are associated with therapy resistance, can be identified. This enables the early adjustment of treatment and has the potential to significantly enhance clinical outcome. The application of ctDNA in early breast cancer is an ongoing investigation. In (neo)adjuvant settings, there is preliminary data indicating that ctDNA can be used for therapy monitoring and risk stratification to decide on post-neoadjuvant strategies. In the monitoring of aftercare, the detection of ctDNA appears to be several months ahead of routine imaging. However, the feasibility of implementing this approach in a clinical setting remains to be seen. While the use of ctDNA as a screening method for the asymptomatic population would be highly advantageous due to its minimally invasive nature, the available data on its clinical benefit are still insufficient. Nevertheless, ctDNA represents the most promising avenue for fulfilling this potential future need.
近年来，液体活检尤其是循环肿瘤DNA（ctDNA）领域取得的进展，对乳腺癌治疗、监测及早期检测具有开创性意义。游离DNA（cfDNA）是由各类细胞释放到血液中的循环DNA片段，其中源自恶性细胞并携带特定基因突变的cfDNA被称为ctDNA。ctDNA分析为疾病诊断、疗效监测及耐药性检测提供了微创手段。目前ctDNA分析方法多样，各具优势与局限：定量聚合酶链式反应作为成熟技术，因其高灵敏度与特异性被广泛用于已知突变检测；多基因分析技术则可同步检测包括罕见突变在内的多种基因变异。这些方法具有互补性，可根据临床需求进行策略性选择。 在转移性乳腺癌领域，ctDNA能动态监测肿瘤演变，展现出独特价值。通过ctDNA分析可识别与治疗耐药相关的ESR1或PIK3CA基因突变，从而早期调整治疗方案，有望显著改善临床预后。在早期乳腺癌中的应用尚处探索阶段：新辅助/辅助治疗场景的初步数据显示，ctDNA可用于疗效监测与风险分层，指导新辅助治疗后策略制定；术后监测中ctDNA检测较常规影像学可提前数月提示复发迹象，但其临床实施可行性仍需验证。虽然ctDNA因其微创特性作为无症状人群筛查工具具有显著优势，但目前关于其临床获益的数据仍不充分。尽管如此，ctDNA仍是满足未来潜在筛查需求最具前景的研究方向。
Circulating Tumor DNA in Early and Metastatic Breast Cance—Current Role and What Is Coming Next
肿瘤(癌症)患者之家