Role of combined chemo- and immunotherapy in early breast cancer

Cancer treatment is often based on combined locoregional and systemic therapy in order to achieve a maximum disease-free and overall survival rate with lowest toxic side-effects. Although a multidisciplinary treatment package is offered, up to 25% of early breast cancer patient will develop metastases in spite of optimal treatment. Tumour resistance to systemic therapy and dysregulation of the host-anti-tumour immune response have been linked with disease recurrence and metastases. In addition, the beneficial effects and synergistic effect of combined chemo-immunotherapy in a phased regimen have been shown in lung cancer, but not have been comprehensively/fully studied in early stages of breast cancer (BC).

In the first part of this study, we will perform a pre-clinical research project to study the expression of immune checkpoints (ICPs e.g. PD-1) in hormone receptor negative (ER/PR negative) tumours.  Secondly, we will conduct a phase 0 window-of-opportunity-study to evaluate the potential synergistic effect of combined chemo- and immunotherapy (using anti-PD 1 antibodies) in early stage disease of BC. This study will provide more insight in the potential role of immunity, and phased chemo- and immunotherapy in early breast cancer. Thereby our results might open new therapeutic pathways in the treatment of early ER/PR negative BC, as well as criteria to evaluate therapy response. Additionally, by the identification of predictive biomarkers of therapy response, we will be able to select patients that are eligible for immune modulation therapy, combined with chemotherapy if indicated.