Mulder Charlotta V, Jongbloed Elisabeth M, Liefaard Marte C, Makrodimitris Stavros, Hazelaar Daan M, Beaufort Corine M, de Weerd Vanja, Mulder Lennart, van Deurzen Carolien H M, Sonke Gabe S, Jager Agnes, Wilting Saskia M, Martens John W M, Jansen Maurice P H M, Lips Esther H
Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Breast Cancer Res. 2025 Jul 1;27(1):120. doi: 10.1186/s13058-025-02077-8.
Early prediction of the response to neoadjuvant chemotherapy (NAC) enables tailoring treatment strategies to the specific needs of individual breast cancer patients. Circulating tumor DNA (ctDNA) has shown to be a prognostic factor for response on NAC during treatment. However, at this point in time mostly tumor-informed ctDNA detection methods are used which are costly, have relatively long turnaround times and are subsequently potentially less feasible for widespread clinical application. In this study, we investigated four tumor-agnostic methods to determine their ability to accurately detect circulating tumor DNA (ctDNA) at baseline. These methods were the Oncomine Breast cell free DNA (cfDNA) NGS panel, the LINE-1 sequencing assay mFAST-SeqS, shallow whole genome sequencing and the genome-wide methylation profiling assay MeD-Seq. In total 40 patients with triple negative or luminal B breast cancer were included and cell free DNA (cfDNA) from plasma before the start of NAC was analyzed with the four assays. We detected ctDNA in 3/24 (12.5%) patients with Oncomine, 5/40 (12.5%) with mFast-SeqS, 3/40 (7.7%) with low pass shallow WGS and 23/40 with MeD-Seq (57.5%). When all methods were combined ctDNA was detected in 65% of patients. In conclusion, we demonstrated that tumor agnostic methods, in particular MeD-Seq, can detect ctDNA in a fraction of the patients with early breast cancer, but further optimization is needed to reach the potential currently demonstrated by tumor-informed methods.
新辅助化疗（NAC）疗效的早期预测有助于根据个体乳腺癌患者的特定需求制定治疗策略。循环肿瘤DNA（ctDNA）已被证明是治疗期间NAC疗效的一个预后因素。然而，目前大多使用的是肿瘤知情的ctDNA检测方法，这些方法成本高昂、周转时间相对较长，因此在广泛的临床应用中可能不太可行。在本研究中，我们调查了四种肿瘤非特异性方法，以确定它们在基线时准确检测循环肿瘤DNA（ctDNA）的能力。这些方法分别是Oncomine乳腺癌游离DNA（cfDNA）二代测序（NGS） panel、LINE-1测序分析mFAST-SeqS、浅层全基因组测序和全基因组甲基化分析MeD-Seq。总共纳入了40例三阴性或管腔B型乳腺癌患者，并使用这四种检测方法分析了NAC开始前血浆中的游离DNA（cfDNA）。我们使用Oncomine在3/24（12.5%）的患者中检测到ctDNA，使用mFast-SeqS在5/40（12.5%）的患者中检测到，使用低通量浅层全基因组测序（WGS）在3/40（7.7%）的患者中检测到，使用MeD-Seq在23/40（57.5%）的患者中检测到。当所有方法联合使用时，在65%的患者中检测到了ctDNA。总之，我们证明了肿瘤非特异性方法，特别是MeD-Seq，可以在一部分早期乳腺癌患者中检测到ctDNA，但需要进一步优化才能达到目前肿瘤知情方法所显示的潜力。
