Abstract P4-02-23: Integrating tumor-intrinsic and immunological factors to improve locoregional treatment individualization of high-risk breast tumors

Abstract Background: The influence of the local immune infiltrate on tumor progression is dependent on tumor-intrinsic characteristics. Among highly aggressive subtypes, an immune infiltrate is associated with a favorable prognostic effect. The aim was to investigate whether the integration of histological grade and degree of tumor-infiltrating lymphocytes (TILs) permits improved treatment individualization for clinically high-risk tumors. Methods: The SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median time of 15.2 years. In total, 8% were treated with systemic therapy. Histological grade and TILs were evaluated on whole-tissue sections by board-certified pathologists. Grade III tumors were compared to grade I and II tumors. TILs were classified as high (>=10%) or low (< 10%). The primary endpoint was ipsilateral breast tumor recurrence (IBTR) within 10 years. Results: In total, 134 (57%) of the 235 grade III tumors had high TIL levels compared to grade I/II tumors where 142 (19.7%) out of 721 tumors exhibited high TIL levels. Grade III tumors with high TILs had a reduced risk of IBTR (HR 0.49, CI 95% 0.26-0.91, p=0.025) compared to grade III tumors with low TILs (HR 1.0). Among grade I/II tumors, high TILs was not prognostic (HR 1.02, CI 95% 0.62-1.68, p=0.95) compared to grade I/II tumors with low TILs (HR 1.0). Grade III tumors with low TILs had a high risk of recurrence without RT (36.2%) and derived benefit from RT (HR 0.16, CI 95% 0.047-0.53, p=0.0029). In contrast, grade III tumors with high TILs had a lower risk of IBTR without RT (14.5%) and did not benefit significantly from RT (HR 0.71, CI 95% 0.26-1.90, p=0.50). Conclusion: Measurements of the local immune infiltrate may improve treatment individualization when integrated with tumor-intrinsic features of aggressivity, such as histological grade. High-risk tumors with an immune infiltrate may be candidates for RT de-escalation. Citation Format: Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrika Killander, Dan Lundstedt, Anikó Kovács, Erik Holmberg, Per Karlsson. Integrating tumor-intrinsic and immunological factors to improve locoregional treatment individualization of high-risk breast tumors [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-23.