Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer
Abstract We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360®, 74 gene next-generation sequencing (NGS) with MBC are identified. We...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-022-00490-2 |
| _version_ | 1797428842790387712 |
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| author | Neelima Vidula Andrew Lipman Shumei Kato Caroline Weipert Katherine Hesler Georges Azzi Ahmed Elkhanany Dejan Juric Estelamari Rodriguez Colleen Faulkner Paul Makhlouf Kristin Price Joyce O’Shaughnessy Aditya Bardia |
| author_facet | Neelima Vidula Andrew Lipman Shumei Kato Caroline Weipert Katherine Hesler Georges Azzi Ahmed Elkhanany Dejan Juric Estelamari Rodriguez Colleen Faulkner Paul Makhlouf Kristin Price Joyce O’Shaughnessy Aditya Bardia |
| author_sort | Neelima Vidula |
| collection | DOAJ |
| description | Abstract We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360®, 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review. The median number of alterations and a median maximum mutant allelic fraction (MAF) in MSI-H and non-MSI-H cohorts are compared with Mann–Whitney U-test. Of 6718 patients with breast cancer with ≥1 plasma NGS alteration, 42 (0.63%) have MSI-H. A median number of genomic alterations per sample is 11 in MSI-H vs. 3 in non-MSI-H (Mann–Whitney U-test p < 0.0001) and the median maximum MAF is 16.8% in MSI-H vs. 2.6% in non-MSI-H (Mann–Whitney U-test p < 0.0001). The co-existing genomic landscape is heterogeneous. The median response duration for seven patients receiving immunotherapy is 92 days (range 29–273 days). CfDNA can identify MSI-H in MBC. Research is needed to validate immunotherapy usage in cfDNA-detected MSI-H MBC. |
| first_indexed | 2024-03-09T09:04:40Z |
| format | Article |
| id | doaj.art-f65bfda34691462a94c380daea7a2c6a |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T09:04:40Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-f65bfda34691462a94c380daea7a2c6a2023-12-02T10:47:32ZengNature Portfolionpj Breast Cancer2374-46772022-11-01811710.1038/s41523-022-00490-2Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancerNeelima Vidula0Andrew Lipman1Shumei Kato2Caroline Weipert3Katherine Hesler4Georges Azzi5Ahmed Elkhanany6Dejan Juric7Estelamari Rodriguez8Colleen Faulkner9Paul Makhlouf10Kristin Price11Joyce O’Shaughnessy12Aditya Bardia13Massachusetts General Hospital Cancer Center, Harvard Medical SchoolFlorida Cancer SpecialistsUniversity of California San DiegoGuardant HealthMassachusetts General Hospital Cancer Center, Harvard Medical SchoolBienes Cancer CenterUniversity of Alabama at BirminghamMassachusetts General Hospital Cancer Center, Harvard Medical SchoolSylvester Comprehensive Cancer Center, University of Miami Miller School of MedicineFlorida Cancer SpecialistsFlorida Cancer SpecialistsGuardant HealthTexas Oncology-Baylor Charles A. Sammons Cancer CenterMassachusetts General Hospital Cancer Center, Harvard Medical SchoolAbstract We evaluate microsatellite instability-high (MSI-H) status with cell-free DNA (cfDNA) in metastatic breast cancer (MBC) and the association with clinico-genomic characteristics. Patients with MSI-H in cfDNA (Guardant360®, 74 gene next-generation sequencing (NGS) with MBC are identified. We conduct a retrospective review. The median number of alterations and a median maximum mutant allelic fraction (MAF) in MSI-H and non-MSI-H cohorts are compared with Mann–Whitney U-test. Of 6718 patients with breast cancer with ≥1 plasma NGS alteration, 42 (0.63%) have MSI-H. A median number of genomic alterations per sample is 11 in MSI-H vs. 3 in non-MSI-H (Mann–Whitney U-test p < 0.0001) and the median maximum MAF is 16.8% in MSI-H vs. 2.6% in non-MSI-H (Mann–Whitney U-test p < 0.0001). The co-existing genomic landscape is heterogeneous. The median response duration for seven patients receiving immunotherapy is 92 days (range 29–273 days). CfDNA can identify MSI-H in MBC. Research is needed to validate immunotherapy usage in cfDNA-detected MSI-H MBC.https://doi.org/10.1038/s41523-022-00490-2 |
| spellingShingle | Neelima Vidula Andrew Lipman Shumei Kato Caroline Weipert Katherine Hesler Georges Azzi Ahmed Elkhanany Dejan Juric Estelamari Rodriguez Colleen Faulkner Paul Makhlouf Kristin Price Joyce O’Shaughnessy Aditya Bardia Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer npj Breast Cancer |
| title | Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer |
| title_full | Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer |
| title_fullStr | Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer |
| title_full_unstemmed | Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer |
| title_short | Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer |
| title_sort | detection of microsatellite instability high msi h status by targeted plasma based genotyping in metastatic breast cancer |
| url | https://doi.org/10.1038/s41523-022-00490-2 |
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