Project 460658

Worldwide, 1 in 8 women will develop breast cancer in the course of their lifetime. Triple-negative breast cancers (TNBC) represent 15-20% of all diagnosed breast cancers and are associated with earlier age of onset and worse overall outcome. Unfortunately, there are currently no specific therapies for TNBC treatment and chemotherapy remains standard of care. One promising therapeutic avenue is to enhance the patient's immune system to destroy tumour cells. Immune cell infiltration can be augmented by newly developed immunotherapies used for other cancers. So far, TNBC patients have not benefited from immunotherapies to the same extent as other cancers. We now understand that alterations within TNBC tumor cells, involving markers called CD73 and B7H4, as well as normal cells in the breast, called cancer associated fibroblasts, play a role in suppressing the immune cells that can attack the tumor. To understand this and develop strategies to enhance the immune response in TNBC patients we need to study large numbers of patients with TNBC and specifically those that are undergoing immunotherapy treatment is well controlled clinical trials. This is only feasible if we include multiple clinical sites such as proposed in this international multisite application. This international team brings together clinical leads of ongoing immunotherapy clinical trials for TNBC, with scientists who have identified alterations in tumor cells (CD73, B7H4) and cancer associated fibroblasts that contribute to an immunosuppressive response. By directly analysing tumor specimens from these clinical trials and by integrating genomic based approaches with the ability of the Canadian team to examine in depth the tumor immune microenvironment will provide the first understanding at scale to improve response of TNBC to immunotherapies.