Abstract LB216: Exploration of optimal synergistic treatment strategies of postoperative radiotherapy and immunotherapy in early-stage breast cancer

Abstract Background: The synergistic effects of radiotherapy (RT) and immunotherapy (IT) in cancer treatment have been increasingly recognized. However, the optimal sequencing and dosing of RT and IT remain unclear for breast cancer patients. This study aims to identify the best synergistic strategy of postoperative RT and IT for early-stage breast cancer. Method: Using the National Cancer Database, HER2-negative early-stage breast cancer patients who underwent surgery followed by RT and IT were selected. Patients were stratified into either RT-first (RI group) or IT-first (IR group) sequences. Propensity score methods were used to balance baseline characteristics. Kaplan-Meier survival analysis and weighted log-rank test evaluated overall survival. Subgroup analyses were conducted. To verify the hypothesis that tumor burden may influence the choice of optimal sequencing, stage IV inoperable patients with higher tumor burden were additionally screened for survival analysis. Results: A total of 3813 patients were included (RI group: 923 (24.2%); IR group: 2890 (75.8%)). Patients in the IR group showed significantly improved survival (p < 0.001). Patients who received adjuvant chemotherapy had improved survival with the IT-first sequence (p<0.001); however, for patients who did not receive adjuvant chemotherapy, there was no difference in survival between the two sequences (p=0.21). Additionally, the conventional RT fractionation regimen combined with the IT-first sequence was associated with better outcomes (p < 0.001), whereas there was no significant difference in outcomes between sequences under the hypofractionated regimen (p=0.20). For patients with stage IV breast cancer, there were no significant difference between the two sequencing (p=0.34). Discussion: Recent studies have shown that RT can remodel tumor microenvironment and damage tumor cells to release tumor-specific antigens, which are more significant in advanced stage patients with high tumor burdens. However, in postoperative early-stage breast cancer patients, a low tumor burden may limit these mechanisms. On the other hand, initiating IT first may reshape the immune microenvironment, thus enabling RT to exert a stronger abscopal effect. This may explain why patients in the IR group showed a better prognosis. Therefore, the optimal RT-IT synergy strategy should consider tumor burden, adjuvant therapies, and RT regimens, since conventional RT fractionation may yield better outcomes. Conclusion: This study found that IT followed by RT may be a better synergistic sequencing for patients with early-stage breast cancer who undergo upfront surgery, especially those receiving adjuvant chemotherapy. Moreover, conventional RT fractionation may be associated with better outcomes. Tumor burden may influence the choice of the optimal strategy, highlighting the need for personalized treatment. Citation Format: Qingyao Shang, Hanyu Wang, Meishuo Ouyang, Fei Ma, Jennifer K. Plichta, Samantha M. Thomas, Youwen He, Xin Wang, Sheng Luo. Exploration of optimal synergistic treatment strategies of postoperative radiotherapy and immunotherapy in early-stage breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB216.