Abstract 5471: Integrating Tumor-Intrinsic and Immunological Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort; Results from the Randomized SweBCG91RT Trial

Purpose: The local immune infiltrate’s influence on tumor progression may be linked to tumor-intrinsic factors. This study aimed to investigate whether integrating immunological and tumor-intrinsic factors could identify patients who may be candidates for de-escalation of radiotherapy (RT).Experimental Design: The practice-changing SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT with sparse use of systemic therapy (95% without systemic therapy) and followed for a median time of 15.2 years. We developed two gene expression models to capture immunological activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could identify a subgroup where RT de-escalation is feasible. Results: The immunomodulatory model correlated with proliferation and was named Proliferative Index. The immunological model was enriched for T cell signatures and was named Immunescore. Increased Proliferative Index predicted an increased prognostic benefit from Immunescore (pinteraction=0.01). Combining the two models stratified patients who may be recommended an escalated RT (RT boost) by RT benefit and prognosis. Patients with a low predicted risk benefited from standard RT (HR: 0.28, CI 95% 0.09-0.85, p=0.025) and had a 5.4% 10-year incidence of ipsilateral breast tumor recurrence (IBTR) after radiation. In contrast, the group with a high predicted risk, characterized by rapidly proliferating tumors without an immune infiltrate, had a clinically meaningful high 10-year incidence of IBTR despite RT treatment (19.5% (CI 95% 12.2-30.3)). Conclusions: Integrating tumor-intrinsic and immunological factors may identify immunogenic tumors in early-stage breast cancer populations and identify patients for whom de-escalated RT may be appropriate. Patients with rapidly proliferating tumors and an immune infiltrate may be candidates for RT de-escalation. Citation Format: Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrik Killander, Laura Chang, Felix Y. Feng, Corey W. Speers, Lori J. Pierce, Anokó Kovács, Dan Lundstedt, Erik Holmberg, Per Karlsson. Integrating tumor-intrinsic and immunological factors to identify immunogenic breast cancers from a low-risk cohort; results from the randomized SweBCG91RT trial. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5471.