Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy
Abstract Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2− breast cancer patients receiving endocrine and CDK4/6 inhi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00783-2 |
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| author | Jesús Fuentes-Antrás Mitchell J. Elliott Sasha C. Main Philippe Echelard Aaron Dou Philippe L. Bedard Eitan Amir Michelle B. Nadler Nicholas Meti Nancy Gregorio Elizabeth Shah Emily Van de Laar Celeste Yu Yangqing Deng Lisa Gates Clodagh Murray Christopher G. Smith Amber Chevalier Scott V. Bratman Lillian L. Siu Hal K. Berman David W. Cescon |
| author_facet | Jesús Fuentes-Antrás Mitchell J. Elliott Sasha C. Main Philippe Echelard Aaron Dou Philippe L. Bedard Eitan Amir Michelle B. Nadler Nicholas Meti Nancy Gregorio Elizabeth Shah Emily Van de Laar Celeste Yu Yangqing Deng Lisa Gates Clodagh Murray Christopher G. Smith Amber Chevalier Scott V. Bratman Lillian L. Siu Hal K. Berman David W. Cescon |
| author_sort | Jesús Fuentes-Antrás |
| collection | DOAJ |
| description | Abstract Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2− breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design. |
| format | Article |
| id | doaj-art-ae5c6c7f05ee4e8f81f3f3f160bb1a25 |
| institution | DOAJ |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-ae5c6c7f05ee4e8f81f3f3f160bb1a252025-08-20T03:05:07ZengNature Portfolionpj Breast Cancer2374-46772025-07-0111111210.1038/s41523-025-00783-2Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapyJesús Fuentes-Antrás0Mitchell J. Elliott1Sasha C. Main2Philippe Echelard3Aaron Dou4Philippe L. Bedard5Eitan Amir6Michelle B. Nadler7Nicholas Meti8Nancy Gregorio9Elizabeth Shah10Emily Van de Laar11Celeste Yu12Yangqing Deng13Lisa Gates14Clodagh Murray15Christopher G. Smith16Amber Chevalier17Scott V. Bratman18Lillian L. Siu19Hal K. Berman20David W. Cescon21Division of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDepartment of Medical Biophysics, University of TorontoDepartment of Pathology and Laboratory Medicine, University Health NetworkDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoGerald Bronfman Department of Oncology, St. Mary’s Hospital Center, McGill UniversityDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDepartment of Statistics, University of TorontoNeoGenomics, IncNeoGenomics, IncNeoGenomics, IncNeoGenomics, IncDepartment of Medical Biophysics, University of TorontoDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoDepartment of Pathology and Laboratory Medicine, University Health NetworkDivision of Medical Oncology & Hematology, Department of Medicine, Princess Margaret Cancer Centre and University of TorontoAbstract Improved methods to monitor treatment response may enhance patient management and clinical outcomes. This study assessed the feasibility and performance of a tumor-informed circulating tumor DNA (ctDNA) assay in metastatic HR+/HER2− breast cancer patients receiving endocrine and CDK4/6 inhibitor therapy. By conducting whole exome sequencing on archival tumors, highly sensitive personalized ctDNA panels were designed for blood monitoring. The assay showed high detection sensitivity (91% baseline, 70% all timepoints) and associations between higher baseline estimated variant allele fractions, liver metastases, and shorter time to treatment failure (TTF) and overall survival (OS). Complete molecular response, defined as ctDNA clearance, was observed in 28% of patients and correlated with improved TTF (HR 0.07) and OS (HR 0.07). The last cleared timepoint predated treatment failure by a median 14.3 months. ctDNA rises or limited decreases preceded radiographic progression. Molecular metrics may facilitate plasma-first monitoring and innovative strategies for clinical practice and trial design.https://doi.org/10.1038/s41523-025-00783-2 |
| spellingShingle | Jesús Fuentes-Antrás Mitchell J. Elliott Sasha C. Main Philippe Echelard Aaron Dou Philippe L. Bedard Eitan Amir Michelle B. Nadler Nicholas Meti Nancy Gregorio Elizabeth Shah Emily Van de Laar Celeste Yu Yangqing Deng Lisa Gates Clodagh Murray Christopher G. Smith Amber Chevalier Scott V. Bratman Lillian L. Siu Hal K. Berman David W. Cescon Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy npj Breast Cancer |
| title | Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy |
| title_full | Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy |
| title_fullStr | Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy |
| title_full_unstemmed | Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy |
| title_short | Personalized ctDNA monitoring in metastatic HR+/HER2− breast cancer patients during endocrine and CDK4/6 inhibitor therapy |
| title_sort | personalized ctdna monitoring in metastatic hr her2 breast cancer patients during endocrine and cdk4 6 inhibitor therapy |
| url | https://doi.org/10.1038/s41523-025-00783-2 |
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