Clinical validity of repeated circulating tumor cell enumeration as an early treatment monitoring tool for metastatic breast cancer in the PREDICT global pooled analysis

Abstract Purpose: The aim of PREDICT was to confirm clinical validity and the potential for clinical utility of serial circulating tumor cell (CTC) enumeration in metastatic breast cancer (MBC) patients focusing on its prognostic value in different breast cancer subtypes and clinical settings. Experimental design: In total, 4436 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. Results: Using the cutoff ≥ 1 CTC for CTC positivity, 913 (20.6%) patients had 0 CTCs at both time points (neg/neg), 325 (7.3%) and 1189 (26.8%) patients converted from CTC negative to CTC positive (neg/pos) or vice versa (pos/neg), while 2009 (45.3%) patients had at least one CTC at both time points (pos/pos). 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 to CTC non-responders (pos/pos) (HR 0.48, 95% CI 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. Conclusions: 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 MBC are urgently needed.