Immunotherapy for the treatment of breast cancer: Checkpoint blockade, cancer vaccines, and future directions in combination immunotherapy

Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte–associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers. Specifically, overall response rates of 19% with PD-1/PD-L1–directed antibodies have been reported in 2 small studies of women with PD-L1–positive, heavily pretreated advanced triple-negative breast cancer. In combination with nab-paclitaxel, confirmed response rates were 46% in a PD-L1–unselected population in the first-line metastatic triple-negative breast cancer setting. Checkpoint-blocking antibodies also have been evaluated in small studies of women with hormone receptor-positive metastatic breast cancer, and in women whose breast cancers lack PD-L1 expression, with more modest response rates. It has been hypothesized that some breast cancers are not inherently recognized by the immune system; however, preclinical and preliminary clinical data suggest that inherently modest immunogenicity may be overcome with novel vaccination strategies, as well as strategies that combine immune checkpoint blockade with methods of optimizing antigen presentation, such as tumor ablation, radiation, chemotherapy, or other approaches. If ongoing registrational trials support the use of immunotherapy, it could revolutionize the care of early-stage and metastatic breast cancer, and ideally improve cure rates.