The Role of checkpoint blockade in the management of early stage breast cancer

Abstract

The classical treatment regimen for early stage breast cancer is surgery, systemic adjuvant therapy, and radiation therapy. This approach has resulted in significant reduction in the rates of breast cancer recurrence and mortality but approximately 20% of patients still suffer cancer recurrence or death. Novel strategies are being developed to harness the immune system and generate tumor specific immune responses with the potential to provide long-term cancer control and improve cure rates. These strategies hold great promise for therapeutic innovation. The successful development of immune checkpoint targeting molecules such as programmed cell death-1 (PD-1), PD-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have resulted in improved directed therapies across a range of different tumor types including melanoma, lung, bladder, kidney, head and neck, Merkel cell, and Hodgkin’s lymphoma. Unfortunately, only modest responses to checkpoint blockade therapy have been reported in metastatic breast cancer, although exceptionally positive responses are observed on rare occasions. Overall response rates improve considerably when checkpoint blockade therapy is administered in combination with other strategies such as chemotherapy indicating the potential for combination strategies to improve breast cancer cure rates. In this article, we describe some of the strategies being explored in ongoing immune therapy clinical trials treating early stage breast cancer.