Some challenges are the heterogeneity and dynamic changes of PD-L1 expression in the tumor microenvironment, PD-L1 expression may vary between primary tumors and metastases, and in breast cancer immunotherapy trials, there were multiple assays for each antibody, multiple scoring systems, and different cut-offs to define PD-L1 positivity (99). This evidence concerns the gene CD274 and breast carcinoma.