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This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+\u2009CTCs), <jats:italic>ESR1<\/jats:italic>\/<jats:italic>PIK3CA<\/jats:italic> mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Ninety-seven patients with HR+\u2009mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC<jats:sup>\u00ae<\/jats:sup> and EpCAM or c-MET CTC isolation kits. <jats:italic>PIK3CA<\/jats:italic> and <jats:italic>ESR1<\/jats:italic> hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the <jats:italic>ESR1<\/jats:italic> mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (<jats:italic>p<\/jats:italic>\u2009=\u20090.00002). Survival analysis showed that c-MET+\u2009CTC, cfDNA concentration, and <jats:italic>ESR1<\/jats:italic> mutations were significantly associated with poor prognosis (<jats:italic>p<\/jats:italic>\u2009=\u20090.0026, 0.0021, and 0.0064, respectively) in HR+\/HER2\u2212 mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and <jats:italic>PIK3CA<\/jats:italic> mutations were not associated with progression-free survival (PFS) in HR+\/HER2\u2212 mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+\/HER2\u2212 mBC.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Monitoring c-MET+\u2009CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+\u2009CTC count and cfDNA concentration could provide complementary information on disease progression in HR+\u2009\/HER2\u2212 mBC, highlighting the importance of integrated liquid biopsy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13058-024-01768-y","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T16:03:26Z","timestamp":1705593806000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive\/HER2-negative metastatic breast cancer"],"prefix":"10.1186","volume":"26","author":[{"given":"Jieun","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sol","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaithanya","family":"Chelakkot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjung","family":"Sung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungsoo","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hye","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Young","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyegyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ran","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Jeong","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kee","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon Hee","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon-La","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,18]]},"reference":[{"key":"1768_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00573","author":"MM Haque","year":"2019","unstructured":"Haque MM, Desai KV. 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