Genomic landscape of breast cancer in elderly patients
Abstract Breast cancer (BC) displays age-related histopathologic and transcriptomic heterogeneity. Whether BC in elderly patients differs genetically from that of younger individuals remains unclear. We re-analyzed sequencing data from 1918 BCs previously subjected to an FDA-cleared paired tumor-nor...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00781-4 |
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| author | Pier Selenica Higinio Dopeso Matteo Repetto Thais Basili Andrea M. Gazzo Christopher J. Schwartz Fatemeh Derakhshan Antonio Marra Lorenzo Ferrando Regina G. H. Beets-Tan Y. H. Wen Dara S. Ross Edi Brogi Hong Zhang Larry Norton Sarat Chandarlapaty Pedram Razavi Diana Mandelker Jorge S. Reis-Fiho Britta Weigelt Fresia Pareja |
| author_facet | Pier Selenica Higinio Dopeso Matteo Repetto Thais Basili Andrea M. Gazzo Christopher J. Schwartz Fatemeh Derakhshan Antonio Marra Lorenzo Ferrando Regina G. H. Beets-Tan Y. H. Wen Dara S. Ross Edi Brogi Hong Zhang Larry Norton Sarat Chandarlapaty Pedram Razavi Diana Mandelker Jorge S. Reis-Fiho Britta Weigelt Fresia Pareja |
| author_sort | Pier Selenica |
| collection | DOAJ |
| description | Abstract Breast cancer (BC) displays age-related histopathologic and transcriptomic heterogeneity. Whether BC in elderly patients differs genetically from that of younger individuals remains unclear. We re-analyzed sequencing data from 1918 BCs previously subjected to an FDA-cleared paired tumor-normal targeted sequencing assay across elderly (≥65 years), middle-aged (>45 and <65 years) and young (≥45 years) patients. BCs in elderly individuals exhibited fewer germline but were numerically enriched in somatic homologous recombination deficiency (HRD)/DNA damage response (DDR) genetic alterations. Primary ER+/HER2- BC in elderly patients showed shifts in the spectrum of actionable PI3K/AKT alterations, whereas metastatic cases were enriched in FAT1 and RB1 mutations and fewer ESR1 mutations, suggesting age-dependent therapeutic resistance mechanisms. Metastatic ER+/HER2- lobular BCs were enriched in actionable ERBB2 mutations. Resistance-associated alterations were more prevalent in metastatic vs primary BC in elderly patients. Our findings reveal distinct actionable genetic features in elderly patients, highlighting the importance of genomic profiling and treatment personalization in this population. |
| format | Article |
| id | doaj-art-0ef1bc29cdf3474981d8b0bcb602c7fa |
| institution | DOAJ |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-0ef1bc29cdf3474981d8b0bcb602c7fa2025-08-20T03:05:07ZengNature Portfolionpj Breast Cancer2374-46772025-07-0111111010.1038/s41523-025-00781-4Genomic landscape of breast cancer in elderly patientsPier Selenica0Higinio Dopeso1Matteo Repetto2Thais Basili3Andrea M. GazzoChristopher J. Schwartz4Fatemeh Derakhshan5Antonio Marra6Lorenzo Ferrando7Regina G. H. Beets-Tan8Y. H. Wen9Dara S. Ross10Edi Brogi11Hong Zhang12Larry Norton13Sarat Chandarlapaty14Pedram Razavi15Diana Mandelker16Jorge S. Reis-Fiho17Britta Weigelt18Fresia Pareja19Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterGROW School for Oncology and Developmental Biology, University of MaastrichtDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Breast Service, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Breast Service, Memorial Sloan Kettering Cancer CenterDepartment of Medicine, Breast Service, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterAbstract Breast cancer (BC) displays age-related histopathologic and transcriptomic heterogeneity. Whether BC in elderly patients differs genetically from that of younger individuals remains unclear. We re-analyzed sequencing data from 1918 BCs previously subjected to an FDA-cleared paired tumor-normal targeted sequencing assay across elderly (≥65 years), middle-aged (>45 and <65 years) and young (≥45 years) patients. BCs in elderly individuals exhibited fewer germline but were numerically enriched in somatic homologous recombination deficiency (HRD)/DNA damage response (DDR) genetic alterations. Primary ER+/HER2- BC in elderly patients showed shifts in the spectrum of actionable PI3K/AKT alterations, whereas metastatic cases were enriched in FAT1 and RB1 mutations and fewer ESR1 mutations, suggesting age-dependent therapeutic resistance mechanisms. Metastatic ER+/HER2- lobular BCs were enriched in actionable ERBB2 mutations. Resistance-associated alterations were more prevalent in metastatic vs primary BC in elderly patients. Our findings reveal distinct actionable genetic features in elderly patients, highlighting the importance of genomic profiling and treatment personalization in this population.https://doi.org/10.1038/s41523-025-00781-4 |
| spellingShingle | Pier Selenica Higinio Dopeso Matteo Repetto Thais Basili Andrea M. Gazzo Christopher J. Schwartz Fatemeh Derakhshan Antonio Marra Lorenzo Ferrando Regina G. H. Beets-Tan Y. H. Wen Dara S. Ross Edi Brogi Hong Zhang Larry Norton Sarat Chandarlapaty Pedram Razavi Diana Mandelker Jorge S. Reis-Fiho Britta Weigelt Fresia Pareja Genomic landscape of breast cancer in elderly patients npj Breast Cancer |
| title | Genomic landscape of breast cancer in elderly patients |
| title_full | Genomic landscape of breast cancer in elderly patients |
| title_fullStr | Genomic landscape of breast cancer in elderly patients |
| title_full_unstemmed | Genomic landscape of breast cancer in elderly patients |
| title_short | Genomic landscape of breast cancer in elderly patients |
| title_sort | genomic landscape of breast cancer in elderly patients |
| url | https://doi.org/10.1038/s41523-025-00781-4 |
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