Copy number profiling by array comparative genomic hybridization identifies frequently occurring BRCA2‐like male breast cancer

Abstract

Genomic aberrations can be used to subtype breast cancer. In this study, we investigated DNA copy number (CN) profiles of 69 cases of male breast cancer (MBC) by array comparative genomic hybridization (aCGH) to detect recurrent gains and losses in comparison with female breast cancers (FBC). Further, we classified these profiles as BRCA1-like, BRCA2-like or non-BRCA-like profiles using previous classifiers derived from FBC, and correlated these profiles with pathological characteristics. We observed large CN gains on chromosome arms 1q, 5p, 8q, 10p, 16p, 17q, and chromosomes 20 and X. Large losses were seen on chromosomes/chromosome arms 1p, 6p, 8p, 9, 11q, 13, 14q, 16q, 17p, and 22. The pattern of gains and losses in estrogen receptor positive (ER+) MBC was largely similar to ER+ FBC, except for gains on chromosome X in MBC, which were uncommon in FBC. Out of 69 MBC patients, 15 patients (22%) had a BRCA2-like profile, of which 2 (3%) were also BRCA1-like. One patient (1%) was only BRCA1-like; the remaining 53 (77%) patients were classified as non-BRCA-like. BRCA2-like cases were more often p53 accumulated than non-BRCA-like cases (P = 0.014). In conclusion, the pattern of gains and losses in ER+ MBC was largely similar to that of its ER+ FBC counterpart, except for gains on chromosome X in MBC, which are uncommon in FBC. A significant proportion of MBC has a BRCA2-like aCGH profile, pointing to a potentially hereditary nature, and indicating that they could benefit from a drug regimen targeting BRCA defects as in FBC.

The molecular genetic make-up of male breast cancer

“…Recent large-scale cross-platform projects have provided a detailed characterization of the genomic landscape of FBC (Cancer Genome Atlas Network 2012, Curtis et al 2012, Nik-Zainal et al 2016, Pereira et al 2016, Bailey et al 2018, Berger et al 2018. The Cancer Genome Atlas (TCGA) (Cancer Genome Atlas Network 2012) reported the enrichment of specific mutations in PIK3CA (47%), GATA3 (14%), MAP3K1 (13%), TP53 (12%), CDH1 (10%) and MAP2K4 (7%) with the luminal A subtype and in TP53 (31%), PIK3CA (32%) and MAP3K1 (5%) within the luminal B subtype (Gao et al 2015).…”

A review of estrogen receptor/androgen receptor genomics in male breast cancer

“…A recent study of similar size (59 MBC samples) also found that MBCs and FBCs of similar subtype shared many recurrent copy number aberrations (Piscuoglio et al 2016). Unfortunately, this study did not determine BRCA2-like status based on copy number profiles despite reporting 5% of the samples as germline BRCA2 mutated, so validation of high frequency of BRCA2-like status in MBC (Biesma et al 2015) and potential AR upregulation could not be investigated.…”

“…In a recent study, Biesma and coworkers found 22% of MBC samples investigated (15/69) had a BRCA2-like profile based on DNA copy number data indicating a significant proportion of MBCs may be susceptible to PARP inhibition therapy or specific chemotherapy regimens aimed at DNA double-strand breaks (Biesma et al 2015). In addition, with the exception of gains on chromosome X in MBC, this work found few differences between MBC and FBC (luminal-like) with respect to copy number changes (Biesma et al 2015). This is a particularly interesting finding as AR is found on chromosome X and may therefore be upregulated in these samples.…”

Association Between BRCA Status and P53 Status in Breast Cancer: A Meta-Analysis

“…However, the relationship between P53 expression and BRCA2 Mut is less clear than that for BRCA1 Mut . Biesma et al [ 37 ] identified P53 overexpression in approximately 50% of BRCA2 Mut , whereas others reported that less than 20% of such tumors had elevated P53 [ 38 ]. Additionally, P53 overexpression was not found in BRCA2 Mut tumors in 1 report [ 39 ].…”