Schwartz Christopher J, Genco Iskender, Repetto Matteo, Muldoon Daniel, Gazzo Andrea, Terraf Panieh, Grabenstetter Anne, Ross Dara, Zhang Hong, Mandelker Diana, Powell Simon, Weigelt Britta, Bandlamudi Chaitanya, Brogi Edi, Pareja Fresia, Wen Hannah Y
Memorial Sloan Kettering Cancer Center.
Res Sq. 2025 Jun 11:rs.3.rs-6680831. doi: 10.21203/rs.3.rs-6680831/v1.
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.
与微腺性腺病相关的浸润性乳腺癌（IBC-MGA）是三阴性乳腺癌（TNBC）的一种罕见且特征不明的形式。我们分析了38例患者的临床、病理和种系遗传数据，其中包括34例IBC-MGA和4例原位病例。在42%（16/38）的患者中发现了同源重组缺陷（HRD）基因的种系致病或可能致病变异，主要存在于BRCA1基因中（81%，13/16）。大多数肿瘤为3级浸润性导管癌或化生癌，肿瘤浸润淋巴细胞较少。在种系HRD相关病例和散发病例之间未观察到显著的临床病理差异。配对的肿瘤-正常靶向测序显示TP53频繁突变且HRD评分较高。这些发现强调了与MGA相关的乳腺癌与HRD相关种系变异之间的关系，并突出了靶向治疗策略的潜力以及基因检测在这一罕见TNBC亚组中的重要性。
