Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials
Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (C...
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| Format: | Article |
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Wiley
2025-07-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13675 |
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| author | Nikolai Kragøe Andresen Andreas Hagen Røssevold Elin Borgen Cecilie Bendigtsen Schirmer Bjørnar Gilje Øystein Garred Jon Lømo Marius Stensland Oddmund Nordgård Ragnhild Sørum Falk Randi R. Mathiesen Hege G. Russnes Jon Amund Kyte Bjørn Naume |
| author_facet | Nikolai Kragøe Andresen Andreas Hagen Røssevold Elin Borgen Cecilie Bendigtsen Schirmer Bjørnar Gilje Øystein Garred Jon Lømo Marius Stensland Oddmund Nordgård Ragnhild Sørum Falk Randi R. Mathiesen Hege G. Russnes Jon Amund Kyte Bjørn Naume |
| author_sort | Nikolai Kragøe Andresen |
| collection | DOAJ |
| description | Immune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy. Programmed death‐ligand 1 (PD‐L1) expression on CTCs was also measured. Patients with ≥ 2 CTCs per 7.5 mL at baseline had gene expression profiles in tumor suggestive of increased T‐cell activity, including increased tumor inflammation signature (TIS) in both triple‐negative (P = 0.010) and hormone receptor‐positive (P = 0.024) disease. Patients with luminal A BC had higher CTC levels. The association between CTC status and outcome was most apparent 4 weeks into therapy. PD‐L1 expression in CTCs was observed in 6/17 CTC‐positive patients and was associated with inferior survival. In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy. |
| format | Article |
| id | doaj-art-d9cb39efb3ac45b4a90bee6aaa9a165e |
| institution | DOAJ |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-d9cb39efb3ac45b4a90bee6aaa9a165e2025-08-20T03:17:43ZengWileyMolecular Oncology1574-78911878-02612025-07-011972092210810.1002/1878-0261.13675Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trialsNikolai Kragøe Andresen0Andreas Hagen Røssevold1Elin Borgen2Cecilie Bendigtsen Schirmer3Bjørnar Gilje4Øystein Garred5Jon Lømo6Marius Stensland7Oddmund Nordgård8Ragnhild Sørum Falk9Randi R. Mathiesen10Hege G. Russnes11Jon Amund Kyte12Bjørn Naume13Department of Clinical Cancer Research Oslo University Hospital NorwayDepartment of Clinical Cancer Research Oslo University Hospital NorwayDepartment of Pathology Oslo University Hospital NorwayDepartment of Pathology Oslo University Hospital NorwayDepartment of Hematology and Oncology Stavanger University Hospital NorwayDepartment of Pathology Oslo University Hospital NorwayDepartment of Pathology Oslo University Hospital NorwayDepartment of Hematology and Oncology Stavanger University Hospital NorwayDepartment of Hematology and Oncology Stavanger University Hospital NorwayOslo Centre for Biostatistics and Epidemiology Oslo University Hospital NorwayDepartment of Oncology Oslo University Hospital NorwayInstitute of Clinical Medicine University of Oslo NorwayDepartment of Clinical Cancer Research Oslo University Hospital NorwayInstitute of Clinical Medicine University of Oslo NorwayImmune checkpoint inhibitors (ICIs) have been introduced in breast cancer (BC) treatment and better biomarkers are needed to predict benefit. Circulating tumor cells (CTCs) are prognostic in BC, but knowledge is limited on CTCs in the context of ICI therapy. In this study, serial sampling of CTCs (CellSearch system) was evaluated in 82 patients with metastatic BC enrolled in two randomized trials investigating ICI plus chemotherapy. Programmed death‐ligand 1 (PD‐L1) expression on CTCs was also measured. Patients with ≥ 2 CTCs per 7.5 mL at baseline had gene expression profiles in tumor suggestive of increased T‐cell activity, including increased tumor inflammation signature (TIS) in both triple‐negative (P = 0.010) and hormone receptor‐positive (P = 0.024) disease. Patients with luminal A BC had higher CTC levels. The association between CTC status and outcome was most apparent 4 weeks into therapy. PD‐L1 expression in CTCs was observed in 6/17 CTC‐positive patients and was associated with inferior survival. In conclusion, our study indicates that CTC numbers may inform on tumor immune composition, as well as prognosis. These findings suggest a potential of using CTCs as an accessible biomarker source in BC patients treated with immunotherapy.https://doi.org/10.1002/1878-0261.13675breast cancercirculating tumor cellsimmune checkpoint inhibitorsliquid biopsy |
| spellingShingle | Nikolai Kragøe Andresen Andreas Hagen Røssevold Elin Borgen Cecilie Bendigtsen Schirmer Bjørnar Gilje Øystein Garred Jon Lømo Marius Stensland Oddmund Nordgård Ragnhild Sørum Falk Randi R. Mathiesen Hege G. Russnes Jon Amund Kyte Bjørn Naume Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials Molecular Oncology breast cancer circulating tumor cells immune checkpoint inhibitors liquid biopsy |
| title | Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials |
| title_full | Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials |
| title_fullStr | Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials |
| title_full_unstemmed | Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials |
| title_short | Circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors – a biomarker analysis of the ALICE and ICON trials |
| title_sort | circulating tumor cells in metastatic breast cancer patients treated with immune checkpoint inhibitors a biomarker analysis of the alice and icon trials |
| topic | breast cancer circulating tumor cells immune checkpoint inhibitors liquid biopsy |
| url | https://doi.org/10.1002/1878-0261.13675 |
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