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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Breast Cancer
Online Access:https://doi.org/10.1038/s41523-025-00794-z
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Summary: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.
ISSN:2374-4677