Abstract P4-07-15: Tumor infiltrating lymphocytes as a prognostic factor
Authors: Schüler Kathleen , Bethmann Daniel , Lantzsch Tilmann , Uleer Christoph , Hanf Volker , Peschel Susanne , John Jutta , Pöhler Marleen , Buchmann Joerg , Buerrig Karl-Friedrich , Weigert Edith , Kantelhardt Eva Johanna , Thomssen Christoph , Vetter Martina 
Published: March 2022

Abstract
Introduction. Tumor cells are influenced by their microenvironment, including immune infiltration. These tumor infiltrating lymphocytes (TILs) are considered to have prognostic and predictive value for patients with early breast cancer. The aim of this study was to evaluate the distribution of TILs and the association with survival in unselected sample of breast cancers. Patients and Methods. From a prospective, multicenter cohort of 1,270 breast cancer patients (PiA, Prognostic Assessment in routine application, NCT 01592825), 1,136 samples were evaluated for TIL infiltration inside the borders of the invasive tumor, following the recommendations of the international TILs working group. TILs were assigned to one of these three TILs groups: low TILs (&lt;10%) intermediate (10-60%) and high TILs (&gt;60%) and additionally scored as a continuous parameter per 10% increment. Primary objective was the distribution of TILs in different groups dependent on hormone receptor and HER2 status of the tumor (IHC group). Second objective was the association of TILs with recurrence free interval (RFI) and overall survival (OS) in univariate and multivariate analyses. The median observation time was 62 months (1-123). Results. Dependent on the IHC types a specific distribution of TILs was found: more than 60% TILs were detected in 1.5% (12 of 828) of hormone receptor (HR) positive and HER2 negative tumors, 9.7% (17 of 175) of HER2 positive tumors with any HR status and 18.8% (25 of 133) of triple negative breast cancer (TNBC). Patients with HR positive and HER2 negative tumors showed no impact of TILs with regard to RFI and OS. In the HER2 positive group with more than 60% TILs, no RFI event was detected, and with less than 60% TILs, 15% of the patients had an RFI event. The probability of OS was 94% (TILs &gt;60%) and 81% (TILS ≤60%). For TNBC and the same TIL cut off, 88% had no RFI and OS event, compared to 70% with no event for RFI and 74% for OS. Applying 10% increments of TILs to the entire cohort, the multivariate analysis revealed a hazard ratio of 0.895 (95% CI 0.796-1.007) for RFI and a significant hazard ratio of 0.890 (95% CI 0.794-0.997) for OS. Considering the IHC groups, a 10% increment of TILs in HER2 positive tumors led to an increase of RFI (0.792, 95% CI 0.601-1.043) and OS (0.713, 95% CI 0.533-0.955, p&lt;0.05) and in TNBC an increase of RFI (0.906, 95% CI 0.773-1.063) and OS (0.941, 95% CI. 0.795-1.115). There was no effect of TILs for patients with HR positive tumors. For the HER2 positive group the highest likelihood of a significant effect was determined for a cut-off of 20% (RFI: 2.467, 95% CI 0.903-6.735, p=0.078; OS: 4.565, 95% CI 1.583-13.159, p=0.005), for TNBC the highest likelihood was found at a cut-off of 5% (RFI: 1.440, 95% CI 0.627-3.308, p=0.390; OS: 2.035, 95% CI 0.906-4.571, p=0.085). Conclusion. Using data from our multicenter, consecutive enrolled cohort, TILs were ascertained as an independent even not significant prognostic factor for patients with HER2 positive and TN tumours. A 10% increment of TILs led to a 21% better disease specific survival (RFI) for patients with HER2-positive tumors and a 10% better RFI for patients with TNBC. Hence, for clinical implementation of prognostic assessment, we would suggest to use 20% as the cut-off for HER2 positive tumors and 5% for TN tumors.
Citation Format: Kathleen Schüler, Daniel Bethmann, Tilmann Lantzsch, Christoph Uleer, Volker Hanf, Susanne Peschel, Jutta John, Marleen Pöhler, Joerg Buchmann, Karl-Friedrich Buerrig, Edith Weigert, Eva Johanna Kantelhardt, Christoph Thomssen, Martina Vetter. Tumor infiltrating lymphocytes as a prognostic factor [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-15.