Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes
Abstract Invasive breast carcinomas associated with microglandular adenosis (IBC-MGA) represent a rare and poorly characterized form of triple-negative breast cancer (TNBC). We analyzed clinical, pathological, and germline genetic data from 38 patients, including 34 IBC-MGAs and 4 in situ cases. Ger...
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Nature Portfolio
2025-07-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00794-z |
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| author | Christopher J. Schwartz Iskender Genco Matteo Repetto Daniel Muldoon Andrea Gazzo Panieh Terraf Anne Grabenstetter Dara Ross Hong Zhang Diana Mandelker Simon Powell Britta Weigelt Chaitanya Bandlamudi Edi Brogi Fresia Pareja Hannah Y. Wen |
| author_facet | Christopher J. Schwartz Iskender Genco Matteo Repetto Daniel Muldoon Andrea Gazzo Panieh Terraf Anne Grabenstetter Dara Ross Hong Zhang Diana Mandelker Simon Powell Britta Weigelt Chaitanya Bandlamudi Edi Brogi Fresia Pareja Hannah Y. Wen |
| author_sort | Christopher J. Schwartz |
| collection | DOAJ |
| description | Abstract Invasive breast carcinomas associated with microglandular adenosis (IBC-MGA) represent a rare and poorly characterized form of triple-negative breast cancer (TNBC). We analyzed clinical, pathological, and germline genetic data from 38 patients, including 34 IBC-MGAs and 4 in situ cases. Germline pathogenic or likely pathogenic variants in homologous recombination-deficiency (HRD) genes were found in 42% (16/38) of patients, predominantly in BRCA1 (81%, 13/16). Most tumors were grade 3 invasive ductal or metaplastic carcinomas with limited tumor-infiltrating lymphocytes. No significant clinicopathologic differences were observed between germline HRD-associated and sporadic cases. Paired tumor-normal targeted sequencing revealed frequent TP53 mutations and high HRD scores. These findings underscore the relationship of breast carcinomas associated with MGA with HRD-related germline variants and highlight the potential for targeted therapeutic strategies and the importance of genetic testing in this rare subset of TNBC. |
| format | Article |
| id | doaj-art-9ad65571d42e4b0d9fb90848d2aec029 |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-9ad65571d42e4b0d9fb90848d2aec0292025-08-20T03:43:20ZengNature Portfolionpj Breast Cancer2374-46772025-07-011111610.1038/s41523-025-00794-zBreast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genesChristopher J. Schwartz0Iskender Genco1Matteo Repetto2Daniel Muldoon3Andrea Gazzo4Panieh Terraf5Anne Grabenstetter6Dara Ross7Hong Zhang8Diana Mandelker9Simon Powell10Britta Weigelt11Chaitanya Bandlamudi12Edi Brogi13Fresia Pareja14Hannah Y. Wen15Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterDepartment of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer CenterEarly Drug Development Service, Department of 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 CenterDepartment of Radiation Oncology, 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 CenterAbstract Invasive breast carcinomas associated with microglandular adenosis (IBC-MGA) represent a rare and poorly characterized form of triple-negative breast cancer (TNBC). We analyzed clinical, pathological, and germline genetic data from 38 patients, including 34 IBC-MGAs and 4 in situ cases. Germline pathogenic or likely pathogenic variants in homologous recombination-deficiency (HRD) genes were found in 42% (16/38) of patients, predominantly in BRCA1 (81%, 13/16). Most tumors were grade 3 invasive ductal or metaplastic carcinomas with limited tumor-infiltrating lymphocytes. No significant clinicopathologic differences were observed between germline HRD-associated and sporadic cases. Paired tumor-normal targeted sequencing revealed frequent TP53 mutations and high HRD scores. These findings underscore the relationship of breast carcinomas associated with MGA with HRD-related germline variants and highlight the potential for targeted therapeutic strategies and the importance of genetic testing in this rare subset of TNBC.https://doi.org/10.1038/s41523-025-00794-z |
| spellingShingle | Christopher J. Schwartz Iskender Genco Matteo Repetto Daniel Muldoon Andrea Gazzo Panieh Terraf Anne Grabenstetter Dara Ross Hong Zhang Diana Mandelker Simon Powell Britta Weigelt Chaitanya Bandlamudi Edi Brogi Fresia Pareja Hannah Y. Wen Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes npj Breast Cancer |
| title | Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes |
| title_full | Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes |
| title_fullStr | Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes |
| title_full_unstemmed | Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes |
| title_short | Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes |
| title_sort | breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination deficiency genes |
| url | https://doi.org/10.1038/s41523-025-00794-z |
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