Primary tumor resection for initially staged IV breast cancer: An emphasis on programmed death-ligand 1 expression, promoter methylation status, and survival

Conventional therapy modalities for advanced breast cancer are problematic, whereas checkpoint blockade immunotherapy has been considered as a promising approach. This study aims to determine programmed death-ligand 1 (PD-L1) expression and methylation status of PD-L1 promoter in primary tumor tissue and metastatic foci of patients with stage IV breast cancer. Clinicopathological data and survival rates of 57 breast cancer patients, who were initially staged IV, and operated for intact tumors, were retrospectively analyzed. Immunohistochemical analysis of PD-L1 using 57 primary tumors, 33 paired metastatic lymph nodes, and 14 paired distant metastases was performed. Additionally, the methylation rate of the PD-L1 gene promoter region was determined with real-time polymerase chain reaction (PCR) analysis in 38 samples. Overall PD-L1 expression in primary tumors was 23.1% (12/52). PD-L1 positivity was reduced in lymph nodes by 15.2% (5/33) and in distant metastases by 21.4% (3/14). PD-L1 expression diverged between primary and metastatic foci in a subset of cases (18.2% for lymph node and 33.3% for distant metastasis). In general, the PD-L1 promoter was not methylated, and mean methylation rates were low (min. 0%–max. 21%). We observed no correlation between PD-L1 expression, promoter methylation, and survival. Neither the expression nor the methylation status of PD-L1 in patients, who were presented with stage IV breast cancer and operated for an intact primary tumor, had a statistically significant relation with survival. Discordance in PD-L1 expression between primary tumor and metastasis should be considered during pathological and clinical management of patients who would undergo checkpoint blockade therapy.