Braun Tatjana, Huesmann Sophia, Pfister Kerstin, Friedl Thomas W P, Hartkopf Andreas, Pantel Klaus, Mehmeti Forca, Mergel Franziska, Schäffler Henning, Heublein Sabine, Wiesmüller Lisa, Rack Brigitte, Fasching Peter A, Janni Wolfgang, Fink Angelina
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Institute of Women's Health, University Hospital Tübingen, Tübingen, Germany.
PLoS One. 2025 Sep 9;20(9):e0331203. doi: 10.1371/journal.pone.0331203. eCollection 2025.
Current aftercare in breast cancer survivors aims to detect local recurrences or contralateral disease, while the detection of distant metastases has not been a central focus due to a lack of evidence supporting an effect on overall survival. However, the data underpinning these guidelines are mainly from trials of the 1980s/1990s and have not been updated to reflect the significant advancements in diagnostic and therapeutic options that have emerged over the past 40 years. In this trial, the aim is to test whether a liquid biopsy-based detection of (oligo-) metastatic disease at an early pre-symptomatic stage followed by timely treatment can impact overall survival compared to current standard aftercare.
In this partially double-blinded superiority study, intensified liquid biopsy-guided surveillance will be assessed versus standard surveillance in medium-to-high-risk early breast cancer patients. Intensive surveillance comprises 3-monthly tests of circulating free tumor DNA (ctDNA), circulating tumor cells (CTC) and serum tumor markers CEA, CA 27.29 and CA125. Upon positivity of biomarker and/or symptoms, staging examinations are initiated. In total, 3500 patients will be randomized in a 1:1 ratio after completion of primary antineoplastic therapy. Co-primary endpoints are overall survival (OS) and the overall lead time effect. The trial will be accompanied by an extensive translational research program.
A risk-based aftercare and regular screening for asymptomatic metastatic disease with molecular markers in the absence of any radiological findings can potentially revolutionize current follow-up care of breast cancer survivors and enable potential treatment even before patients suffer from symptomatic, incurable disease.
目前乳腺癌幸存者的后续护理旨在检测局部复发或对侧疾病，而由于缺乏支持对总生存期有影响的证据，远处转移的检测并非核心重点。然而，支撑这些指南的数据主要来自20世纪80年代/90年代的试验，并未更新以反映过去40年中出现的诊断和治疗选择的重大进展。在本试验中，目的是测试与当前标准后续护理相比，在症状前早期基于液体活检检测（寡）转移性疾病并及时治疗是否会影响总生存期。
在这项部分双盲优效性研究中，将对中高危早期乳腺癌患者强化液体活检引导的监测与标准监测进行评估。强化监测包括每3个月检测循环游离肿瘤DNA（ctDNA）、循环肿瘤细胞（CTC）以及血清肿瘤标志物癌胚抗原（CEA）、糖类抗原27.29（CA 27.29）和癌抗原125（CA125）。一旦生物标志物呈阳性和/或出现症状，即开始进行分期检查。在完成一线抗肿瘤治疗后，总共3500名患者将按1:1的比例随机分组。共同主要终点是总生存期（OS）和总体领先时间效应。该试验将伴随一个广泛的转化研究项目。
基于风险的后续护理以及在无任何影像学发现的情况下使用分子标志物对无症状转移性疾病进行定期筛查，可能会彻底改变目前乳腺癌幸存者的后续护理，并使患者在出现有症状的不治之症之前就有可能接受治疗。
