Abstract P1-04-10: Association of stromal tumor infiltrating lymphocytes (sTILs) in pretreatment biopsies in different molecular subtypes of HER2+/ER+ breast cancer: Assessment of NRG Oncology/NSABP B-52

Abstract Background: The primary aim of the NRG Oncology/NSABP B-52 clinical trial was to test if estrogen deprivation (ED) administered concomitantly with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP), would improve the pCR rate in patients with HER2+/ER+ early breast cancer. A numerical increase in the pCR rate was observed with ED (46.1% v 40.9%), but the difference was not statistically significant. The purposes of this study were to assess the association of sTILs in pretreatment biopsies with pCR in the total population and within the molecular subtypes of breast cancer and to assess changes in sTILs between pre- and on-treatment biopsies. The secondary endpoints of recurrence-free interval (RFI) and overall survival (OS) are currently being analyzed and will be presented along with association of these endpoints with sTILs in pretreatment biopsies in the total cohort and within molecular subtypes. Methods: Scoring of sTILs on routine H&E slides from pre-treatment biopsies with sufficient tumor from 249 of the 315 patients (79%) entered in B-52 were performed by one of two pathologists (SKM, RSM). Both pathologists scored sTILs on a subset of 64 patients to document concordance. Wilcoxon two-sided test, box and whisker plots, and forest plots were used to assess associations with pCR. Molecular subtypes were determined utilizing RNA-seq data and AIMS subtyping method. On-treatment biopsies were available in 46 patients and were scored and compared to paired baseline samples. Results: Good concordance between pathologists was established with an inter-pathologist difference of ˂20% difference between scores in 92% of cases. sTILs in pre-treatment samples were associated with pCR across both arms of the trial (p=0.0074) and in the TCHP+ED arm (p=0.033), but not in the TCHP arm (p=0.093). The distribution of intrinsic subtypes was 34% luminal B, 29% luminal A, 28% HER2E, 5.8% normal, and 2.7% basal, with no significant differences between the arms. Presence of sTILs showed a trend for association with pCR in HER2E pre-treatment samples (p=0.054) but not in non-HER2E (p=0.75). Similarly, sTILs were associated with pCR in non-luminal tumors (p=0.055) but not in luminal tumors (p=0.44). Stratification by treatment arm and menopausal status suggested sTILs are associated with pCR in premenopausal women treated with TCHP (OR: 1.04, 95% CI=1.00-1.09). Interestingly, decreases in the sTIL scores with treatment were associated with pCR in the TCHP+ED arm (p=0.01) but not in the TCHP arm. Analysis of RFI and OS on B-52 is ongoing and will be presented along with associations of sTILs with intrinsic subtypes for RFI and OS. Conclusions: Although a positive correlation between sTILs and pCR was observed, the clinical utility appears limited because of the extensive overlap in the TIL scores between pCR and non-pCR tumors. Significance for a positive association of sTILs with pCR was detected in HER2E but not in luminal tumors. This may be due to the molecular differences of the subtypes, or the make-up of the TILs, or both. The association of a decrease in sTILs with TCHP+ED treatment needs further investigation. The small number of samples is a limitation of the study; however, the B-52 protocol specified that the collection of the B-52 samples was for the purpose of exploratory analysis. Our results highlight the molecular heterogeneity of the HER+/ER+ patient population and suggests that different treatment strategies may be required in future treatment regimens for this patient population. Support: NSABP Foundation; BCRF; 3U10CA180868-03S2, -180822; UG1CA189867; Genentech. Citation Format: Katherine L. Pogue-Geile, Sai K. Maley, Rim S. Kim, Ying Wang, Roberto Salgado, Corey Lipchik, Huichen Feng, Reena S. Cecchini, Samuel A. Jacobs, Ashok Srinivasan, Eleftherios (Terry) Mamounas, Charles E. Geyer Jr, Priya Rastogi, C. Kent Osborne, Soonmyung Paik, Norman Wolmark, Peter C. Lucas, Mothaffar Rimawi. Association of stromal tumor infiltrating lymphocytes (sTILs) in pretreatment biopsies in different molecular subtypes of HER2+/ER+ breast cancer: Assessment of NRG Oncology/NSABP B-52 [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 P1-04-10.