Abstract Background: Patients with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC) have a higher risk of recurrence and worse survival outcomes. Prior studies have shown that higher stromal tumor-infiltrating lymphocytes (sTILs) post-NAC in patients with residual TNBC is associated with improved survival outcomes. In this secondary analysis of EA1131, we evaluated the association between sTILs, intrinsic subtype, and invasive disease-free survival (iDFS), stratified by race in patients with residual TNBC after completion of NAC. Patients and methods: EA1131 enrolled patients with clinical stage II or III TNBC with ≥1.0 cm residual disease (RD) in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine on days 1-14 of a 21-day cycle for six cycles. Stromal TIL density was assessed on full-face hematoxylin and eosin (H30% vs. ≥30%) and tumor intrinsic subtype (basal vs. non-basal): (1) low sTILs/basal, (2) low sTILs/non-basal, (3) high sTILs/basal, and (4) high sTILs/non-basal. Cox proportional hazard models were used to examine the association between sTILs and intrinsic subtype group and iDFS, adjusting for available baseline factors. The association between sTILs category and race and intrinsic subtype were examined using Fisher exact test. Results: Among 410 participants with TNBC and RD, H30%); only 23 (7%) had high sTILs (30-50%: n=17; 51-70%: n=3; 70%: n=3). There was no difference in sTILs by intrinsic subtype (p=0.31) or race (p=0.5). Compared to all groups, patients with low TILs and basal subtype (n=244) had the worst iDFS (p=0.005) and had numerically worse OS (p=0.084). Other significant risk factors for iDFS in this group included high histologic grade (vs intermediate and low), positive lymph node (vs negative), higher pathologic T stage (as a continuous variable). Differences according to race could not be analyzed due to small sample size. Conclusion: In the EA1131 clinical trial, patients with residual basal-like TNBC and low sTILs had the worse iDFS, delineating a particularly high-risk subgroup. These findings underscore the prognostic relevance of post-treatment immune microenvironment characteristics and suggest that patients with basal-like, TIL-low residual TNBC may derive limited benefit from current standard adjuvant therapies. Further investigation is warranted to identify and develop tailored therapeutic approaches for this biologically aggressive subgroup to improve long-term outcomes. Citation Format: S. S. Badve, F. Zhao, S. Reid, Y. Gokmen-Polar, I. Mayer, C. L. Arteaga, W. F. Symmans, B. H. Park, B. L. Burnette, D. F. Makower, M. Block, M. A. Kimberly, C. R. Jani, C. Mescher, S. J. Dewani, B. Tawfik, B. Tawfik, L. E. Flaum, E. L. Mayer, W. M. Sikov, E. T. Rodler, A. M. DeMichele, J. A. Sparano, A. C. Wolff, K. D. Miller, ECOG-ACRIN. Tumor infiltrating lymphocytes in post-NACT residual tumors in ECOG-ACRIN EA1131 - impact of intrinsic subtypes abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF3-06.
Badve et al. (2026) studied this question.