Breast carcinomas associated with microglandular adenosis are linked to germline alterations in homologous recombination-deficiency genes

TL;DR

A rare type of triple-negative breast cancer linked to microglandular adenosis is often associated with genetic mutations in HRD genes, suggesting potential for targeted therapies.

Contribution

This study identifies a high frequency of germline HRD gene mutations in IBC-MGA, a rare breast cancer subtype.

Findings

42% of patients had germline pathogenic variants in HRD genes, mostly in BRCA1.

Tumors showed TP53 mutations and high HRD scores, indicating homologous recombination deficiency.

No significant clinicopathologic differences were found between germline HRD-associated and sporadic cases.

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.

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