{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:24Z","timestamp":1785473964024,"version":"3.56.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Patients with hormone receptor\u2013positive (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\n                      <jats:sup>\u00ae<\/jats:sup>\n                      platform to detect molecular precursors of late recurrence in long-term breast cancer survivors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Blood samples from 25 breast cancer patients in recurrence-free survival (RFS), 4\u201313 years post-surgery, were analyzed using the GenoCTC\n                      <jats:sup>\u00ae<\/jats:sup>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, CTCs were detected in 24% of patients. CTC burden was significantly associated with recurrence (P &amp;lt;.0001) and mortality (P\u00a0= .0016). A high CTC count was identified in all recurrence events (P\u00a0= .003). In longitudinal follow-up, 6 of 8 (75%) initially CTC-negative patients demonstrated \u201cmolecular conversion\u201d characterized by a \u201cburst\u201d of epithelial-mesenchymal hybrid CTCs, including CK+\/Vimentin+ and cMET+ populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Longitudinal phenotypic CTC profiling could identify a pre-clinical \u201cmolecular conversion\u201d 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1903915","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:25:01Z","timestamp":1785471901000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.3389","volume":"16","author":[{"given":"Chaithanya","family":"Chelakkot","sequence":"first","affiliation":[{"name":"Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipin Shankar","family":"Chelakkot","sequence":"additional","affiliation":[{"name":"Department of Cancer Science, Cleveland Clinic Research","place":["Cleveland, OH, United States"]},{"name":"Case comprehensive Cancer Center, Case Western Reserve University","place":["Cleveland, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyehyung","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Dong-Eui University","place":["Busan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaeyeol","family":"Cho","sequence":"additional","affiliation":[{"name":"Research Institute, Genobio Corp","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Park","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayeong","family":"Hong","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Institute, Cichlid Corporation","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kee","family":"Shin","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Science, Department of Pharmacy, Seoul National University College of Pharmacy","place":["Seoul, Republic of Korea"]},{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701830","article-title":"20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years","volume":"377","author":"Pan","year":"2017","journal-title":"N 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