Breast cancer in men is a rare disease, with a higher mortality compared with breast cancer in women. Inherited mutations in BRCA1/2 predispose to male breast cancer (MBC) and may characterize a subgroup of tumors with a peculiar phenotype.
Increasing evidence suggest gender-specific differences in breast cancer, in terms of biological and clinical behavior. However, due to the rarity of the disease, clinical management and therapeutic options of male breast cancer patients has been informed almost entirely by female breast cancer research. Thus, there is an urgent need to obtain further evidence on the molecular basis of this rare disease and how to best treat male patients.
The aim of this project is to dissect MBC immunophenotypes, using an integrating approach, which will include omics, clinical and pathologic data, in order to identify patients that may benefit from personalized treatment.
To investigate the immune landscape in MBC, expression of known immune checkpoint markers and immune cell infiltration profiling will be investigated from transcriptomic data obtained by tumor RNA sequencing. The role of genetic and pathology features in determining specific immunophenotypes will be analyzed by integrating all biomolecular data with clinical and survival information.
Our study, integrating transcriptomic and clinical-pathologic data, will provide insights into key molecular classification of breast cancer which will facilitate the characterization of actionable strategies for MBC patients. The identification of subgroups of patients who deserve specific, individualized clinical management will address an urgent and unmet clinical need in MBC and have profound impact on our approach to this rare disease.
Advancing immunotherapy to a more central and applicable role in breast cancer remains a high priority. A deeper understanding of the immunobiology of breast cancer is considered a critical step toward eventual clinical success of these therapies.
Breast tumors have been long considered immunologically quiescent, with the exception of triple negative breast cancers, a very rare breast cancer subtype in men. Our preliminary data indicate that there is a subset of male patients whose breast cancers with luminal phenotypes present immunogenic characteristics. Results from this study may provide new insights to better understand the male-specific molecular features of BC, highlighting novel immune-related biomarkers, and facilitate the characterization of actionable strategies for MBC patients, not extrapolated from the female counterpart. In addition, male breast tumors, being mainly of luminal type, may help in investigate the prognostic and predictive value of immune-related biomarkers in the ER+/PR+ BC subgroup. Analyzing tumor immune-profiles by genetic factors such as BRCA1/2 mutation status could provide additional insights to better stratify patients eligible for a personalized management.
Current technologies are accelerating new discoveries about tumor molecular characteristics, which could soon translate into more targeted treatments. Our scientific premise is that the identification of gender-specific molecular features of BC, with particular regard to immunophenotypes, will have profound impact on understanding breast cancer biology and will provide a strong evidence base for the potential clinical translation of findings, with a positive impact on individualized medicine for both male and female breast cancer patients.
Breast cancer is a practical example of how personalized medicine is not always guaranteed, since male patients with breast cancer often reported poorer quality of life, during and after treatment, and a greater stigma, along with documented disparities in outcomes. These issues suggest the necessity to address the management of breast cancer on a perspective of gender medicine, in order to meet a proper equality in breast cancer care.
This study aims to ensure an increase in gender-oriented breast cancer information in the medical and scientific communities, to eventually inform future studies addressing the gender perspective in cancer research, and dissemination of information and awareness to the public.
The new knowledge generated by this project can undoubtedly be extended to other research lines, applied to other cancer types and translated into the clinics. In this context, results from this study may eventually inform further research addressing the gender perspective in oncology.