Carnevali Ileana, Tedaldi Gianluca, Pensotti Valeria, Sahnane Nora, Micello Donata, Rovera Francesca, Sessa Fausto, Tibiletti Maria Grazia
Unit of Pathology, Ospedale di Circolo, Azienda Socio Sanitaria Territoriale (ASST)-Sette Laghi, Varese, Italy.
Research Center for the Study of Hereditary and Familial Tumors, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Front Oncol. 2022 May 24;12:891426. doi: 10.3389/fonc.2022.891426. eCollection 2022.
Lobular breast carcinoma (LBC) is considered an exceptionally rare disease in men, including only 1% of all male breast malignancies. The majority of LBCs have negative immunohistochemical staining for E-cadherin () expression, and the loss of function was traditionally implicated in the tumorigenesis of diffuse gastric cancer as well as LBC. It is well recognized that LBC in women could be involved in both hereditary breast and ovarian cancer (HBOC) and hereditary diffuse gastric cancer (HDGC) syndromes; however, there are no data present in literature about the involvement of male LBC in these inherited conditions.
, , and genes were performed on DNA from peripheral blood using next-generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification analyses. and somatic gene analyses were performed on breast tumoral DNA using the NGS sequencing approach.
Here, we describe two men affected by LBC, the carriers of a pathogenic variant of and genes, respectively. Our data, including somatic and germline results, demonstrate a strong relationship between male LBC and HBOC/HDGC syndromes, excluding a sporadic origin of LBC in these two patients. Male LBC could represent a sentinel cancer for inherited syndrome identification, and early identification of cancer susceptibility could improve cancer prevention both for men and women in these families. The history of the LBC patient carrier of the variant suggests to include male LBC genetic testing criteria and male breast surveillance in HDGC guidelines.
小叶性乳腺癌（LBC）在男性中被认为是一种极为罕见的疾病，仅占所有男性乳腺恶性肿瘤的1%。大多数LBC对E-钙黏蛋白（ ）表达呈免疫组化染色阴性，其功能丧失传统上与弥漫性胃癌以及LBC的肿瘤发生有关。众所周知，女性LBC可能与遗传性乳腺癌和卵巢癌（HBOC）以及遗传性弥漫性胃癌（HDGC）综合征有关；然而，文献中尚无关于男性LBC与这些遗传疾病关系的数据。
使用下一代测序（NGS）、桑格测序和多重连接依赖探针扩增分析对外周血DNA进行 、 和 基因检测。使用NGS测序方法对乳腺肿瘤DNA进行 和 体细胞基因分析。
在此，我们描述了两名受LBC影响的男性，分别是 和 基因致病变异的携带者。我们的数据，包括体细胞和种系结果，证明了男性LBC与HBOC/HDGC综合征之间存在密切关系，排除了这两名患者LBC的散发性起源。男性LBC可能是遗传性综合征识别的哨兵癌，早期识别癌症易感性可改善这些家族中男性和女性的癌症预防。 变异的LBC患者携带者的病史提示在HDGC指南中纳入男性LBC基因检测标准和男性乳腺监测。
