The molecular genetic make-up of male breast cancer. Issue 10 (October 2019)

• Record Type: Journal Article
• Authors: Moelans, Cathy B; de Ligt, Joep; van der Groep, Petra; Prins, Pjotr; Besselink, Nicolle J M; Hoogstraat, Marlous; ter Hoeve, Natalie D; Lacle, Miangela M; Kornegoor, Robert; van der Pol, Carmen C; de Leng, Wendy W J; Barbé, Ellis; van der Vegt, Bert; Martens, John; Bult, Peter; Smit, Vincent T H B M; Koudijs, Marco J; Nijman, Isaac J; Voest, Emile E; Selenica, Pier; Weigelt, Britta; Reis-Filho, Jorge S; van der Wall, Elsken; Cuppen, Edwin; van Diest, Paul J
• Is Part Of: Endocrine-related cancer. Volume 26:Issue 10(2019)
• Page Start: 779
• Page End: 794
• Publication Date: 2019-10
• Subjects: breast cancer -- male -- mutation -- copy number -- amplification -- genomic; Endocrine glands -- Cancer -- Periodicals; Endocrinology -- Periodicals; Cancer -- Endocrine aspects -- Periodicals; 616.9944005
• DOI: 10.1530/ERC-19-0278
• Languages: English
• ISSNs: 1351-0088

Abstract

Abstract : Male breast cancer (MBC) is extremely rare and accounts for less than 1% of all breast malignancies. Therefore, clinical management of MBC is currently guided by research on the disease in females. In this study, DNA obtained from 45 formalin-fixed paraffin-embedded (FFPE) MBCs with and 90 MBCs (52 FFPE and 38 fresh-frozen) without matched normal tissues was subjected to massively parallel sequencing targeting all exons of 1943 cancer-related genes. The landscape of mutations and copy number alterations was compared to that of publicly available estrogen receptor (ER)-positive female breast cancers (smFBCs) and correlated to prognosis. From the 135 MBCs, 90% showed ductal histology, 96% were ER-positive, 66% were progesterone receptor (PR)-positive, and 2% HER2-positive, resulting in 50, 46 and 4% luminal A-like, luminal B-like and basal-like cases, respectively. Five patients had Klinefelter syndrome (4%) and 11% of patients harbored pathogenic BRCA2 germline mutations. The genomic landscape of MBC to some extent recapitulated that of smFBC, with recurrent PIK3CA (36%) and GATA3 (15%) somatic mutations, and with 40% of the most frequently amplified genes overlapping between both sexes. TP53 (3%) somatic mutations were significantly less frequent in MBC compared to smFBC, whereas somatic mutations in genes regulating chromatin function and homologous recombination deficiency-related signatures were more prevalent. MDM2 amplifications were frequent (13%), correlated with protein overexpression ( P = 0.001) and predicted poor outcome ( P = 0.007). In conclusion, despite similarities in the genomic landscape between MBC and smFBC, MBC is a molecularly unique and heterogeneous disease requiring its own clinical trials and treatment guidelines.