Clinical trial data and emerging immunotherapeutic strategies: hormone receptor-positive, HER2- negative breast cancer

While checkpoint inhibitors have been approved in patients with newly metastatic PDL1-positive triple negative breast cancer, similar clinical benefit with immunotherapy alone or in combination with chemotherapy has not been observed in patients with hormone receptor-positive, HER2− negative breast cancer in the metastatic setting. However, in the ISPY2 trial, an increase in pathologic response has been observed with the addition of immunotherapy (± PARP inhibition) to chemotherapy compared to chemotherapy alone in patients with high-risk hormone receptor-positive, HER2− breast cancer. We review strategies to enhance the immunotherapeutic activity in this subtype of breast cancer, including combinations of checkpoint inhibition with chemotherapy, endocrine therapy, PARP inhibitors, HDAC inhibitors, CDK4/6 inhibitors, and radiotherapy. Combinations with agents targeting novel immunotherapeutic targets are also discussed. Though there remains an unmet need for immunotherapy approaches in patients with hormone-receptor positive breast cancer, there are a number of approaches that may lead to increased anti-tumor activity with immunotherapy in this tumor subtype.