Funded with support from Sarah Ferguson, The Duchess of York
While there are an increasing number of treatments for breast cancer, a sizeable number of patients develop resistance to these agents and experience disease recurrence. These numerous therapies have been enabled by our deepening understanding of the biology of breast cancer at the molecular and cellular levels, which continues to advance as a result of powerful technologies. To date most treatments have focused on targeting the molecular drivers present within tumor cells, it is increasingly apparent that the effective treatment of aggressive tumors, will necessitate strategies that harness the patient’s immune system to detect and eradicate tumor cells. Such immunotherapies have been highly effective in other tumor types, but their use has lagged breast cancer as this tumor type is thought to be immune cold. Here we perform detailed studies of breast tumor samples from patients enrolled clinical trials evaluating the efficacy of novel targeted and immunotherapeutic strategies in both early-stage and advanced breast cancers with the goal of uncovering the molecular hallmarks of tumors that respond to these agents, as well as those that do not. These studies harness powerful new technologies to study tumor tissue in its native context, while preserving spatial relationship between tumor cells and surrounding immune and stromal cells. This approach will uncover molecular interactions that can be exploited to overcome resistance and to optimize therapies across different subgroups of disease.