Clonality of circulating tumor cells in breast cancer brain metastasis patients
Abstract Background The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13058-019-1184-2 |
| _version_ | 1818426520447746048 |
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| author | Carlotta Riebensahm Simon A. Joosse Malte Mohme Annkathrin Hanssen Jakob Matschke Yvonne Goy Isabell Witzel Katrin Lamszus Jolanthe Kropidlowski Cordula Petersen Anja Kolb-Kokocinski Sascha Sauer Kerstin Borgmann Markus Glatzel Volkmar Müller Manfred Westphal Sabine Riethdorf Klaus Pantel Harriet Wikman |
| author_facet | Carlotta Riebensahm Simon A. Joosse Malte Mohme Annkathrin Hanssen Jakob Matschke Yvonne Goy Isabell Witzel Katrin Lamszus Jolanthe Kropidlowski Cordula Petersen Anja Kolb-Kokocinski Sascha Sauer Kerstin Borgmann Markus Glatzel Volkmar Müller Manfred Westphal Sabine Riethdorf Klaus Pantel Harriet Wikman |
| author_sort | Carlotta Riebensahm |
| collection | DOAJ |
| description | Abstract Background The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. Methods Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). Results CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. Conclusion The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment. |
| first_indexed | 2024-12-14T14:31:08Z |
| format | Article |
| id | doaj.art-9ce323027a994649b8033de0443befc4 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-12-14T14:31:08Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-9ce323027a994649b8033de0443befc42022-12-21T22:57:48ZengBMCBreast Cancer Research1465-542X2019-09-0121111110.1186/s13058-019-1184-2Clonality of circulating tumor cells in breast cancer brain metastasis patientsCarlotta Riebensahm0Simon A. Joosse1Malte Mohme2Annkathrin Hanssen3Jakob Matschke4Yvonne Goy5Isabell Witzel6Katrin Lamszus7Jolanthe Kropidlowski8Cordula Petersen9Anja Kolb-Kokocinski10Sascha Sauer11Kerstin Borgmann12Markus Glatzel13Volkmar Müller14Manfred Westphal15Sabine Riethdorf16Klaus Pantel17Harriet Wikman18Department of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Neuropathology, University Medical Center Hamburg-EppendorfDepartment of Radiotherapy and Radiooncology, University Medical Center Hamburg-EppendorfDepartment of Gynecology, University Medical Center Hamburg-EppendorfDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Radiotherapy and Radiooncology, University Medical Center Hamburg-EppendorfWellcome Sanger InstituteMax Delbrück Center for Molecular Medicine (BIMSB and BIH)Laboratory of Radiobiology and Experimental Radiooncology, University Medical Center Hamburg-EppendorfDepartment of Neuropathology, University Medical Center Hamburg-EppendorfDepartment of Gynecology, University Medical Center Hamburg-EppendorfDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfDepartment of Tumor Biology, University Medical Center Hamburg-EppendorfAbstract Background The incidence of brain metastases in breast cancer (BCBM) patients is increasing. These patients have a very poor prognosis, and therefore, identification of blood-based biomarkers, such as circulating tumor cells (CTCs), and understanding the genomic heterogeneity could help to personalize treatment options. Methods Both EpCAM-dependent (CellSearch® System) and EpCAM-independent Ficoll-based density centrifugation methods were used to detect CTCs from 57 BCBM patients. DNA from individual CTCs and corresponding primary tumors and brain metastases were analyzed by next-generation sequencing (NGS) in order to evaluate copy number aberrations and single nucleotide variations (SNVs). Results CTCs were detected after EpCAM-dependent enrichment in 47.7% of the patients (≥ 5 CTCs/7.5 ml blood in 20.5%). The CTC count was associated with ERBB2 status (p = 0.029) of the primary tumor as well as with the prevalence of bone metastases (p = 0.021). EpCAM-independent enrichment revealed CTCs in 32.6% of the patients, especially among triple-negative breast cancer (TNBC) patients (70.0%). A positive CTC status after enrichment of either method was significantly associated with decreased overall survival time (p < 0.05). Combining the results of both enrichment methods, 63.6% of the patients were classified as CTC positive. In three patients, the matched tumor tissue and single CTCs were analyzed by NGS showing chromosomal aberrations with a high genomic clonality and mutations in pathways potentially important in brain metastasis formation. Conclusion The detection of CTCs, regardless of the enrichment method, is of prognostic relevance in BCBM patients and in combination with molecular analysis of CTCs can help defining patients with higher risk of early relapse and suitability for targeted treatment.http://link.springer.com/article/10.1186/s13058-019-1184-2CTCBreast cancerBrain metastasesClonalityCNANGS |
| spellingShingle | Carlotta Riebensahm Simon A. Joosse Malte Mohme Annkathrin Hanssen Jakob Matschke Yvonne Goy Isabell Witzel Katrin Lamszus Jolanthe Kropidlowski Cordula Petersen Anja Kolb-Kokocinski Sascha Sauer Kerstin Borgmann Markus Glatzel Volkmar Müller Manfred Westphal Sabine Riethdorf Klaus Pantel Harriet Wikman Clonality of circulating tumor cells in breast cancer brain metastasis patients Breast Cancer Research CTC Breast cancer Brain metastases Clonality CNA NGS |
| title | Clonality of circulating tumor cells in breast cancer brain metastasis patients |
| title_full | Clonality of circulating tumor cells in breast cancer brain metastasis patients |
| title_fullStr | Clonality of circulating tumor cells in breast cancer brain metastasis patients |
| title_full_unstemmed | Clonality of circulating tumor cells in breast cancer brain metastasis patients |
| title_short | Clonality of circulating tumor cells in breast cancer brain metastasis patients |
| title_sort | clonality of circulating tumor cells in breast cancer brain metastasis patients |
| topic | CTC Breast cancer Brain metastases Clonality CNA NGS |
| url | http://link.springer.com/article/10.1186/s13058-019-1184-2 |
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