Tegeler Christian Martin, Hartkopf Andreas Daniel, Banys-Paluchowski Maggie, Krawczyk Natalia, Fehm Tanja, Jaeger Bernadette Anna Sophia
Department of Obstetrics and Gynecology, University Hospital Tübingen, 72076 Tübingen, Germany.
Department of Peptide-Based Immunotherapy, Institute of Immunology, University Hospital Tübingen, 72076 Tübingen, Germany.
Cancers (Basel). 2024 Nov 22;16(23):3919. doi: 10.3390/cancers16233919.
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 the or genes, 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,在液体活检尤其是循环肿瘤DNA(ctDNA)方面取得的进展,可被视为乳腺癌治疗、监测和早期检测未来的开创性成果。游离DNA(cfDNA)由各种细胞类型释放到血液中的循环DNA片段组成。这种cfDNA的一部分,即ctDNA,起源于恶性细胞并携带特定的基因突变。对ctDNA的分析为诊断、监测治疗反应和检测耐药性的出现提供了一种微创方法。有几种方法可用于分析ctDNA,每种方法都有独特的优点和局限性。定量聚合酶链反应是一种成熟的技术,因其高灵敏度和特异性而被广泛使用,尤其适用于检测已知突变。除了检测单个突变外,还开发了多基因分析方法,可同时检测多个突变,包括罕见突变。这些方法是互补的,可根据临床问题进行策略性使用。在转移性乳腺癌的背景下,ctDNA具有特别的前景,因为它可以动态监测肿瘤的演变。通过ctDNA分析,可以识别与治疗耐药性相关的 或 基因中的突变。这使得能够早期调整治疗,并有可能显著改善临床结果。ctDNA在早期乳腺癌中的应用正在进行研究。在(新)辅助治疗环境中,有初步数据表明ctDNA可用于治疗监测和风险分层,以决定新辅助治疗后的策略。在随访监测中,ctDNA的检测似乎比常规成像提前几个月。然而,在临床环境中实施这种方法的可行性仍有待观察。虽然由于其微创性质,将ctDNA用作无症状人群的筛查方法将非常有利,但关于其临床益处的现有数据仍然不足。尽管如此,ctDNA代表了满足这一潜在未来需求的最有希望的途径。