Abstract PS4-10-16: Tumor Immune Microenvironment as a Predictive Marker of Neoadjuvant Pembrolizumab Combined with Chemotherapy (KEYNOTE-522 Regimen) Efficacy in Early Triple-Negative Breast Cancer

Abstract Background: The current standard of care based on the KEYNOTE-522(KN522) trial for high-risk early triple-negative breast cancer (TNBC) is neoadjuvant pembrolizumab combined with chemotherapy. Tumor infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) have been identified in multiple solid tumors and are gaining attention as indicators of predictive biomarkers for immune check point inhibitors (ICIs). We report on the relationship between KN522 regimen treatment efficacy and immune microenvironment. Methods: We retrospectively analyzed cStage II-III TNBC patients diagnosed from September 2022 to March 2024 who underwent surgery following neoadjuvant treatment with KN522 regimen. We investigated the TILs and TLS in baseline biopsy samples, histological treatment effect (Strict pCR; ypT0N0, pCR; ypT0/isN0), clinical overall response rate (ORR; CR+PR), and axillary lymph node conversion rate (cN+→ypN0). TILs assessment followed the International Immuno-Oncology Biomarker Working Group guidelines, with lymphocyte-predominant breast cancer (LPBC) defined as TILs occupying ≥50% of the area. TLS was defined as lymphoid follicles with germinal centers. Results: A total of 66 patients were analyzed, with the median age at diagnosis was 51 (25-74) years. cStage II/III comprised 48 cases (73%)/18 cases (27%). TLS was observed in 13 cases (20%), and 19 cases (29%) were LPBC. Univariate analysis showed a mild association between TLS and TILs (p=0.08). Strict pCR/pCR was achieved in 36 cases (55%)/39 cases (59%). While Strict pCR/pCR showed no significant association with TLS (p=0.35/0.53), it was significantly associated with LPBC (p=0.0025/0.0002). The Strict pCR rates for TLS+/LPBC+, TLS-/LPBC+, TLS+/LPBC-, TLS-/LPBC- were 83%(5/6), 85%(11/13), 57%(4/7), and 40%(16/40) respectively. The pCR rates were 83%(5/6), 100%(13/13), 57%(4/7), and 43%(17/40); ORR was 100%(6/6), 100%(13/13), 86%(6/7), and 88%(35/40); and axillary lymph node conversion rates were 100%(3/3), 86%(6/7), 60%(3/5), and 48%(11/23). Conclusion: Cases identified as LPBC in baseline biopsy samples showed high response rates to KN522 regimen. The immune microenvironment profile could be a potential predictive biomarker for ICI containing treatment. Citation Format: N. Yamashita, T. Osako, M. Akiya, Y. Aoyama, Y. Ozaki, M. Nishimura, Y. Haruyama, U. Nakadaira, Y. Kimura, A. lesato, T. Maeda, N. Uehiro, T. Kobayashi, T. Sakai, S. Kitano, T. Takano, T. Ueno. Tumor Immune Microenvironment as a Predictive Marker of Neoadjuvant Pembrolizumab Combined with Chemotherapy (KEYNOTE-522 Regimen) Efficacy in Early Triple-Negative Breast Cancer [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 PS4-10-16.