Janni Wolfgang, Friedl Thomas W P, Yab Tracy C, Bidard Francois-Clément, Cristofanilli Massimo, Hayes Daniel F, Ignatiadis Michail, Regan Meredith M, Alix-Panabieres Catherine, Barlow William E, Caldas Carlos, Carey Lisa A, Dirix Luc, Fehm Tanja, Garcia-Saenz Jose A, Gazzaniga Paola, Generali Daniele, Gerratana Lorenzo, Gisbert-Criado Rafael, Jacot William, Jiang Zefei, Joosse Simon A, Lianidou Evi, López López Rafael, Magbanua Mark J M, Manso Luis, Mavroudis Dimitris, Müller Volkmar, Munzone Elisabetta, Pantel Klaus, Pierga Jean-Yves, Rack Brigitte, Riethdorf Sabine, Rugo Hope S, Sideras Kostandinos, Sleijfer Stefan, Smerage Jeffrey, Stebbing Justin, Terstappen Leon W M M, Vidal-Martínez Jose, Wallwiener Markus, Giridhar Karthik V, Liu Minetta C
Department of Obstetrics and Gynecology, University Hospital Ulm, Ulm, Germany.
Department of Oncology, Mayo Clinic, Rochester, Minnesota.
Clin Cancer Res. 2025 Jun 3;31(11):2196-2209. doi: 10.1158/1078-0432.CCR-24-3108.
The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in patients with metastatic breast cancer, focusing on its prognostic value in different breast cancer subtypes and clinical settings.
In total, 4,436 individual patient-level data with CTC results from both baseline and one follow-up (CellSearch; Menarini Silicon Biosystems) were analyzed to evaluate the association between CTC detection and overall survival (OS) in the full patient cohort and separately for tumor and treatment types.
Using the cutoff ≥1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg) and 325 (7.3%) and 1,189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), whereas 2,009 (45.3%) patients had at least one CTC at both time points (pos/pos). The median OS for the neg/neg, neg/pos, pos/neg, and pos/pos group was 45.6, 26.1, 32.3, and 17.3 months, respectively (P < 0.0001, global log-rank test). CTC responders (pos/neg) showed a lower risk of death compared with CTC nonresponders (pos/pos; HR, 0.48; 95% confidence interval, 0.44-0.53). Similar results were obtained in subgroup analyses according to hormone receptor and HER2 subtype, treatment type, and with a ≥5 CTC cutoff for CTC positivity.
Follow-up CTC assessments strongly predict OS independently from tumor subtype and treatment. New randomized trials to define the clinical utility of CTC monitoring for risk stratification and as an early response marker in metastatic breast cancer are urgently needed.
PREDICT研究旨在证实转移性乳腺癌患者连续循环肿瘤细胞（CTC）计数的临床有效性及临床应用潜力，重点关注其在不同乳腺癌亚型和临床环境中的预后价值。
共分析了4436例患者个体水平的数据，这些数据包含基线期和一次随访期的CTC检测结果（CellSearch；美纳里尼硅生物系统公司），以评估全患者队列以及按肿瘤和治疗类型分组的CTC检测与总生存期（OS）之间的关联。
将CTC阳性的临界值设定为≥1个CTC时，913例（20.6%）患者在两个时间点的CTC均为0（阴性/阴性），325例（7.3%）和1189例（26.8%）患者从CTC阴性转为阳性（阴性/阳性）或反之（阳性/阴性），而2009例（45.3%）患者在两个时间点均至少有1个CTC（阳性/阳性）。阴性/阴性、阴性/阳性、阳性/阴性和阳性/阳性组的中位OS分别为45.6个月、26.1个月、32.3个月和17.3个月（P<0.0001，全局对数秩检验）。与CTC无反应者（阳性/阳性）相比，CTC有反应者（阳性/阴性）的死亡风险更低（风险比，0.48；95%置信区间，0.44 - 0.53）。在根据激素受体和HER2亚型、治疗类型进行的亚组分析中，以及将CTC阳性的临界值设定为≥5个CTC时，均得到了类似结果。
随访CTC评估能独立于肿瘤亚型和治疗方式，有力地预测OS。迫切需要开展新的随机试验，以明确CTC监测在转移性乳腺癌风险分层及作为早期反应标志物方面的临床应用价值。
