Effect of radiotherapy on the residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status in breast cancer patients.

e14034 Background: Preclinical studies have suggested that radiotherapy (RT) followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. RT induces immunogenic changes in cancer cells which can lead to adaptive up-regulation of PD-L1 expression. Moreover, radiotherapy reduces not only local recurrence but also improves overall survival by preventing distant metastases, which indicates its influence on the remaining occult tumor, such as circulating tumor cells. For this reason the aim of this study was to determine the PD-L1 status on CETCs before and during RT. Methods: CETCs were determined in 54 primary breast cancer patients in early and locally advanced stages. The number of CETCs and their expression of PDL-L1 were investigated using the maintrac method. The fraction of PD-L1 positive CETCs was assessed prior to (baseline), 3 and 6 weeks after the start of radiotherapy. Results: We found a correlation between the PD-L1 status of CETCs and aggressiveness of cancer disease prior to radiotherapy. Patients with positive lymph node status presented more PD-L1 positive CETCs compared to patients with negative lymph nodes (mean 73% vs. 50%, p < 0.01). Moreover, the HER2 expression of the primary tumor was also positively correlated with PD-L1 expression. Lower numbers of CETCs were detected in patients who had not received chemotherapy or adjuvant chemotherapy before RT than in those who received neoadjuvant chemotherapy (median 20 vs 25 vs 120 CETC/100µl blood, p < 0.001). Surprisingly, the fraction of PD-L1 positive CETCs decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy. Conclusions: Although the number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy, radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients.