A narrative review of combination therapy of PD-1/PD-L1 blockade with standard approaches for the treatment of breast cancer: clinical application and immune mechanism

Objective: In this review, we aimed to discuss the efficacy of immunotherapy of anti-programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) and potential immune mechanism combination with various standard systemic therapies for breast cancer (BC) such as chemotherapy, targeted therapy, endocrine therapy, and radiotherapy. Background: Single-drug therapy of antibodies against PD-1 and its ligand, PD-L1, have only presented modest responses in patients with BC, partly due to the deficiency of tumor-infiltrating lymphocytes (TILs) and low mutation burden. Thus, the combinations of PD-1/PD-L1 blockade with other approaches which may increase the immune therapy effect are being studied. Moreover, an understanding of the immune mechanism of PD-1/PD-L1 blockade with other approaches will contribute to better application of clinical therapy. Methods: We searched the studies that focus on PD-1/PD- L1 therapy with or without other systemic therapy and relative immune mechanisms indicated between 2000 and 2020. Conclusions: Anti PD-1/L1 blockade combined with therapeutic approaches is safe and effective in BC, in particular for PD-L1 antibody atezolizumab plus nab-paclitaxel by inducing PD-1/L1 expression and the number of cytotoxic T cells. Otherwise, the toxicity also exists during clinical treatment. Future researches should be evaluated to explore the immune mechanism and vast clinical trials need to be conducted for evidential support for combination therapy of BC.