c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer
Abstract Background Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circu...
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BMC
2024-01-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-024-01768-y |
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| author | Jieun Park Eun Sol Chang Ji-Yeon Kim Chaithanya Chelakkot Minjung Sung Ji-Young Song Kyungsoo Jung Ji Hye Lee Jun Young Choi Na Young Kim Hyegyeong Lee Mi-Ran Kang Mi Jeong Kwon Young Kee Shin Yeon Hee Park Yoon-La Choi |
| author_facet | Jieun Park Eun Sol Chang Ji-Yeon Kim Chaithanya Chelakkot Minjung Sung Ji-Young Song Kyungsoo Jung Ji Hye Lee Jun Young Choi Na Young Kim Hyegyeong Lee Mi-Ran Kang Mi Jeong Kwon Young Kee Shin Yeon Hee Park Yoon-La Choi |
| author_sort | Jieun Park |
| collection | DOAJ |
| description | Abstract Background Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions Monitoring c-MET+ CTC, 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+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy. |
| format | Article |
| id | doaj-art-2ca855b356e643debe6b235758b1b02b |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-2ca855b356e643debe6b235758b1b02b2025-01-12T12:45:28ZengBMCBreast Cancer Research1465-542X2024-01-0126111710.1186/s13058-024-01768-yc-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancerJieun Park0Eun Sol Chang1Ji-Yeon Kim2Chaithanya Chelakkot3Minjung Sung4Ji-Young Song5Kyungsoo Jung6Ji Hye Lee7Jun Young Choi8Na Young Kim9Hyegyeong Lee10Mi-Ran Kang11Mi Jeong Kwon12Young Kee Shin13Yeon Hee Park14Yoon-La Choi15Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan UniversityDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineTechnical Research Center, Genobio Corp.Laboratory of Molecular Pathology and Theranostics, Samsung Medical Center, Sungkyunkwan University School of MedicineLaboratory of Molecular Pathology and Theranostics, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of MedicineLaboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityR&D Center, ABION Inc.R&D Center, ABION Inc.Central Laboratory, LOGONE Bio-Convergence Research FoundationR&D Center, Gencurix Inc.Vessel-Organ Interaction Research Center (MRC), College of Pharmacy, Kyungpook National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of MedicineDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan UniversityAbstract Background Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). Methods Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. Results The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2− mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2− mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2− mBC. Conclusions Monitoring c-MET+ CTC, 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+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2− mBC, highlighting the importance of integrated liquid biopsy.https://doi.org/10.1186/s13058-024-01768-yMetastatic breast cancerCirculating tumor cellsPrognostic biomarkersc-METCell-free DNA |
| spellingShingle | Jieun Park Eun Sol Chang Ji-Yeon Kim Chaithanya Chelakkot Minjung Sung Ji-Young Song Kyungsoo Jung Ji Hye Lee Jun Young Choi Na Young Kim Hyegyeong Lee Mi-Ran Kang Mi Jeong Kwon Young Kee Shin Yeon Hee Park Yoon-La Choi c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer Breast Cancer Research Metastatic breast cancer Circulating tumor cells Prognostic biomarkers c-MET Cell-free DNA |
| title | c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer |
| title_full | c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer |
| title_fullStr | c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer |
| title_full_unstemmed | c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer |
| title_short | c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer |
| title_sort | c met positive circulating tumor cells and cell free dna as independent prognostic factors in hormone receptor positive her2 negative metastatic breast cancer |
| topic | Metastatic breast cancer Circulating tumor cells Prognostic biomarkers c-MET Cell-free DNA |
| url | https://doi.org/10.1186/s13058-024-01768-y |
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