High-resolution genomic profiling of male breast cancer reveals differences hidden behind the similarities with female breast cancer

Abstract

Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC subgroup, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male-simple subgroup appears notably different from any genomic subgroup so far defined in FBC.

High proliferation is associated with inferior outcome in male breast cancer patients

“…In a paper characterizing male breast cancer tumors by comparative genomic hybridization, two distinct subgroups could be identified, which differed from genomic subgroups of female breast cancer. 5 Tumors in the larger male breast cancer subgroup displayed complex genomic profiles, significantly higher proliferation and were associated with a poor outcome. In the other study, characterizing male breast cancer tumors by gene expression, two male breast cancer subgroups largely corresponding to the comparative genomic hybridizationbased groups were identified.…”

“…In line with these data, comparative genomic hybridization demonstrated significant differences regarding DNA aberrations compared with female breast cancer, and a new subgroup unique for male patients was identified. 5 Taking all these factors into account, these findings indicate that male breast cancer might be a separate tumor entity from female breast cancer.…”

“…Nevertheless, in two recent studies investigating male breast cancer tumors on the transcriptional and genomic levels, proliferation was one of the most important key biological processes separating the male subgroups. 4,5 Proliferation is driven by the cell cycle, which, in turn, is controlled by rapid (cyclic) changes in the levels of proteins called cyclin. Cyclins A and B are involved in the S-and/or M-phase.…”

A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in Male Breast Cancer

“…The need for more refined therapeutic treatments for male breast cancer (MBC) is evidenced by a steady stream of publications highlighting gender-specific differences using IHC (1-5), genetics (6)(7)(8)(9)(10)(11), and more recently, epigenetics (12)(13)(14)(15). Of note, although MBC is similar histologically to female breast cancer (FBC), with the same panel of biomarkers used to guide treatment and prognosis, more rigorous interrogation of the underlying genetics shows heterogeneity in MBC as recognized in FBC where molecular profiling has identified different subgroups that correlate with varying clinical outcomes.…”

Fibrotic focus and hypoxia in male breast cancer

“…The limited data published on male breast cancer indicate that there are genetic and phenotypic differences between male and female breast cancer. [2][3][4][5][6] Initially, prognosis in men was claimed to be poor with higher incidence of lymph node metastases at the time of discovery, but more recent studies showed that prognosis of male and female breast cancers corrected for stage and age is similar. [7][8][9] Although tumor size and lymph node status are independent prognosticators in male breast cancer, 9,10 there still is a need for more accurate outcome predictors of male breast cancer.…”