Longitudinal monitoring of circulating tumor cell phenotypic conversion as a predictor of late recurrence in breast cancer: a prospective feasibility study using the GenoCTC platform.

Authors

Chaithanya Chelakkot, Vipin Shankar Chelakkot, Hyehyung Shin, Chaeyeol Cho, Jieun Park, Jiu Choi, Dayeong Hong, Hun Seok Lee, Young Kee Shin

Published in

Frontiers in oncology. Volume 16. Pages 1903915. Epub Jul 31, 2026.

Abstract

Patients with hormone receptor-positive (HR+) breast cancer faces a persistent, constant risk of distant recurrence for over 20 years. This proof-of-concept study evaluated the clinical utility of circulating tumor cell (CTCs) monitoring using the GenoCTC^® platform to detect molecular precursors of late recurrence in long-term breast cancer survivors.
Blood samples from 25 breast cancer patients in recurrence-free survival (RFS), 4-13 years post-surgery, were analyzed using the GenoCTC^® platform with EpCAM and Vimentin as markers. Baseline CTCs were characterized by immunofluorescence staining (DAPI+/Cytokeratin (CK)+/CD45-). A subset of eight initially CTC-negative patients underwent longitudinal follow-up assay at a 5-year interval, with expanded profiling including c-MET enrichment. CTCs counts were correlated with clinicopathological variables, receptor status and clinical outcomes.
At baseline, CTCs were detected in 24% of patients. CTC burden was significantly associated with recurrence (P <.0001) and mortality (P = .0016). A high CTC count was identified in all recurrence events (P = .003). In longitudinal follow-up, 6 of 8 (75%) initially CTC-negative patients demonstrated "molecular conversion" characterized by a "burst" of epithelial-mesenchymal hybrid CTCs, including CK+/Vimentin+ and cMET+ populations.
Longitudinal phenotypic CTC profiling could identify a pre-clinical "molecular conversion" in breast cancer survivors, which has the potential to provide a time lead over radiographic appearance of recurrence. Integration of EpCAM, Vimentin and cMET multi-marker CTC monitoring into standard long-term follow-up may enable early interception of dormancy escape and late relapse.

PMID:
42601892
Bibliographic data and abstract were imported from PubMed on 15 Aug 2026.

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