Abstract LB-95: Gene expression profiling of male breast cancer reveals two subgroups distinct from the intrinsic subtypes of female breast cancer

Abstract

Abstract Male breast cancer (MBC) is a rare disease. High-throughput molecular profiling techniques have to date rarely been applied to MBC and the few available studies report small sample sizes; there is hence a paucity of knowledge of the disease at the molecular level. The aim of this study was to characterize 66 clinicopathologically well-annotated fresh frozen MBC tumors by gene expression profiling using Illumina's HumanHT-12 arrays and to compare them with female breast cancer (FBC). Two stable clusters were detected, luminal M1 (70%) and luminal M2 (30%), respectively; additional subgroups may exist, but the limited sample size prevented further subgroupings. Seven gene expression (GEX) modules associated with key biological processes in FBC (tumor invasion and metastasis, immune response, angiogenesis, apoptosis, proliferation, and ER and HER2 signaling, respectively) were used to discover biologically meaningful differences between the two subgroups found in MBC, and to compare them with the intrinsic subgroups of FBC. The luminal M1 tumors were more highly correlated to the tumor invasion and metastasis, proliferation and HER2 modules. Furthermore, patients whose tumors were highly correlated to the tumor invasion and metastasis module had a significantly worse distant metastasis free survival (p=0.02). Genes involved in epithelial-to-mesenchymal transition (EMT), e.g. SLUG, were included in the tumor invasion and metastasis module, and the expression of SLUG was significantly higher in the luminal M1 tumors compared to luminal M2 tumors (p=7x10-5). The majority of MBC tumors in the present study were ER positive by immunohistochemistry, a well-known feature of MBC. Despite this, luminal M1 tumors displayed a significantly lower correlation to the ER signaling module, as well as a more aggressive phenotype and worse prognosis compared luminal M2 tumors. Interestingly, SLUG expression is associated with the basal subtype of FBC. When the MBC subgroups described herein were compared with the intrinsic subgroups of FBC, they differed substantially. Taking this into consideration, combined with the inferior outcome of MBC patients, these findings clearly indicate the requirement to better understand the pathobiology of MBC, and the need to stratify patients based on tumor characteristics, as well as the potential need for alternative treatment strategies for these patients. To summarize, we have revealed two transcriptional subgroups of MBC with different tumor biological features of potential clinical relevance, and also show that MBC differs from FBC. This study was supported by grants from the Swedish Cancer Society, the G Nilsson Cancer Foundation, the Mrs. B Kamprad Foundation, and the Lund University Hospital Research Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-95. doi:1538-7445.AM2012-LB-95