Abstract P4-01-14: Influence of radiotherapy on residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status in breast cancer patients

Abstract

Abstract Background: Preclinical studies have suggested that radiotherapy followed by immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy. Radiation 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 even more distant relapse indicating its influence also on the residual 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 radiotherapy. 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 an association between the PD-L1 status on CETCs and aggressiveness of cancer disease before radiotherapy. Patients with positive lymph node status had more PD-L1 positive CETCs as compared to patients with negative lymph nodes (mean 73 vs. 50, p<0.01). 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 radiation 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 CETC decreased during radiotherapy only in patients who had received neoadjuvant chemotherapy. Conclusion: The number of CETCs and the fraction of PD-L1 positive CETCs were higher in patients who had received neoadjuvant chemotherapy and radiotherapy reduced both measured biomarkers. In the future PD-1/PD-L1 checkpoint inhibitors after radiotherapy might have additional benefit in breast cancer patients. Citation Format: Dorothea Schott, Monika Pizon, Ulrich Pachmann, Katharina Pachmann, Matthias Mäurer. Influence of radiotherapy on residual circulating epithelial tumor cells (CETCs) and their programmed cell death ligand 1 (PD-L1) status in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-14.