Germline Investigation in Male Breast Cancer

Although rare, is breast cancer in males genetic? Researchers provide details. 

Breast cancer is males is rare, accounting for less than 1% of all breast cancer cases. Researchers recently published a study in Breast Cancer Research and Treatment, detailing the profiles of 81 male patients with breast cancer.

In the cohort of 81 patients, the most prevalent pehnotype was NST (87%), though other phentypes were reported as well (7.4%); the majority of tumors were grade 3 carcinomas (52%) and the most common subtype in the study was luminal. Researchers observed high ER/PR expressions, as commonly seen in these studies. In the wider community, family history of breast cancer or ovarian cancer is reported in some 20% of the male breast cancer patients. In this cohorot, some 37% of the participants (30/81) had a breast and ovarian cancer history among first-degree relatives. Genetic counseling history in this group may have led to overrepresentation of family history of cancer.

Researchers performed a germline investigation was via NGS focusing on coding and intron–exon regions of 24 cancer predisposition genes in this well-characterized series of 81 male breast cancer cases. The authors identified 15 variants in 4 genes, and classified them as pathogenic. They then identified 12 variants in 9 genes that were classified as “potentially pathogenic” by a custom pipeline. Finally, they identified 75 rare variants in 20 different genes.

As predicted, the highest rate of pathogenic variants were found in BRCA2 (73.3%, 11/15): 18/81 patients (22.2%).

The authors carried out this study in order to estimate the genetic risk factors for breast cancer in men. The germline investigation screened for all 24 genes involved in breast cancer predisposition. Researchers tested DNA in a custom multi-gene panel that highlightedall coding exons and exonintron boundaries of the 24 genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientifc) and MiSeq (Illumina) platforms. They used a custom pipeline to record all variants. The average age of onset was 61.3 years of age.

The germline mutation found in 22 patients (23%) was in 4 genes: BRCA2, BRIP1, MUTYH and PMS2. The 12 variants of unknown clinical signifcance (VUS) in 9 genes were BARD1, BRCA1, BRIP1, CHEK2, ERCC1, NBN, PALB2, PMS1, and RAD50.