Breast cancer (BC) in men is a rare disease, but morbidity and mortality in male BC (MBC) patients is a serious concern.
Up to 13% of all MBC cases are due to inherited BRCA1 and, more frequently, BRCA2 mutations.
Although MBC shares some similarities with post-menopausal estrogen receptor (ER)-positive female BC (FBC), increasing evidence indicate that MBC may be a heterogeneous disease, different from FBC.
Transcriptome profiling is a valuable approach to identify and deeply characterize BC subgroups of biological and clinical relevance. Based on transcriptome profiles, differentially expressed genes and pathways between BRCA-positive and BRCA-negative have been identified in FBC.
In this research project, we plan on investigating the transcriptome profile of MBC cases characterized for BRCA mutations to confirm and extend our preliminary data indicating different expression patterns between BRCA and non-BRCA MBCs.
Samples and data from the ongoing Italian multicenter study on MBC, will be used to perform a large collaborative study. Transcriptomic profiling of BRCA-positive and BRCA-negative MBC tumors will be performed by RNA sequencing and pathways/genes of interest emerged from the whole transcriptome analysis will be validate in a large independent series.
The characterization of the transcriptional profile of BRCA and non-BRCA MBCs may allow for the identification of specific molecular subgroups of MBCs and could lead to the identification of subtypes that could provide insight into underlying BRCA pathways.
BC in men is a rare and less investigated disease compared with BC in women. Due to its rarity, MBC research and clinical management has been considered similar to FBC management. However, increasing molecular evidence indicate that BC in men and women may behave differently. Thus, there is a need to obtain further evidence on the genetics and biology of this rare disease and how to best treat and support MBC patients.
MBC represents an ideal "model" to improve knowledge of the biology and genetics of BC in general, since it is not affected by confounding factors related to the high frequency of the disease as in females. Investigation of the molecular profiles of BRCA-associated MBCs may help in the identification of specific MBC subgroups with biological and clinical relevance and lead to the characterization of subtypes that could provide insight into underlying BRCA pathways.
Overall, the findings of this research project will be of significant relevance in the clinical management of BC patients of both sexes.