Abstract PS4-10: TNBC-DX Genomic Test Predicts High pCR in Triple-Negative Breast Cancer with sTILs ≥30% Treated with Neoadjuvant Docetaxel-Carboplatin with/without Pembrolizumab

Abstract Background: Stromal tumor-infiltrating lymphocytes (sTILs) and the novel 15-gene TNBC-DX test, which integrates immune, proliferation, tumor size, and nodal status markers, are predictors of pathologic complete response (pCR) in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT), with or without pembrolizumab. This study aimed to evaluate the complementary role of TNBC-DX pCR score and sTILs in predicting pCR in patients receiving NACT ± pembrolizumab. Methods: sTIL quantification and TNBC-DX genomic testing were performed on pretreatment tumor samples from 401 stage I-III TNBC patients undergoing NACT in two clinical trials: MMJ-CAR-2014-01 (NCT01560663; n=292), where patients received 6 cycles of carboplatin plus docetaxel (TCb), and NeoPACT (NCT03639948; n=109), where patients received 6 cycles of TCb + pembrolizumab (TCb+P). sTILs were centrally evaluated. Pre-established cut-offs defined TNBC-DX pCR-low, -medium, and -high groups. Logistic regression models assessed the association of TNBC-DX and sTILs with pCR. Results: In the TCb-treated group, the pCR rate was 49%, with both TNBC-DX pCR score and sTILs associated with pCR (OR per 1-unit increase=1.20, p<0.001 for TNBC-DX; and OR per 1-unit increase=1.01, p<0.001 for sTILs). In the TCb+P group, the pCR rate was 58%, with both TNBC-DX pCR score and sTILs as predictors (OR=1.46, p=0.001 for TNBC-DX; OR=1.27, p=0.001 for sTILs). The correlation between TNBC-DX pCR score and sTILs was weak (r=0.26-0.32). The distribution of TNBC-DX pCR-low, medium, and high groups was approximately one-third for each category across both trials. For TCb, pCR rates in TNBC-DX high, medium, and low groups were 66%, 58%, and 25%, respectively (OR=5.81 for high vs. low; p<0.001). For TCb+P, pCR rates in these groups were 78%, 66%, and 33%, respectively (OR=7.25 for high vs. low; p<0.001). In the sTILs ≥30% and 5-29% subgroups, TNBC-DX was significantly associated with pCR. In the sTILs ≥30% subgroup, the pCR rates for TNBC-DX high, medium, and low were 70%, 65%, and 29%, respectively, for TCb (OR=5.80; p=0.010) and 91%, 79%, and 33%, respectively, for TCb+P (OR=21.0; p<0.001). In the sTILs 5-29% subgroup, the pCR rates for TNBC-DX high, medium, and low were 67%, 60%, and 26% for TCb (OR=5.83; p<0.001) and 64%, 56%, and 14% for TCb+P (OR=21.0; p=0.003). In the sTILs <5% subgroup, the pCR rates for TNBC-DX high, medium, and low were 43%, 44%, and 24% for TCb (OR=2.40; p=0.300) and 33%, 29%, and 40% for TCb+P (OR=0.75; p=0.826). Bivariate analyses showed that both sTILs and TNBC-DX were associated with pCR with TCb+P treatment (sTILs OR=1.23, p=0.005; TNBC-DX OR=1.36, p=0.006), while only TNBC-DX was associated with pCR with TCb treatment (sTILs OR=1.01, p=0.143; TNBC-DX OR=1.18, p<0.001). Overall, tumors with sTILs ≥5% and TNBC-DX pCR med/high scores represented 55-57% of the study population. Conclusions: The TNBC-DX genomic test effectively predicts pCR to neoadjuvant TCb ± pembrolizumab in TNBC. Notably, the TNBC-DX pCR-high group identifies patients with high sTILs who have a pCR rate exceeding 90% when treated with TCb+P. This study confirms that gene expression and sTILs provide distinct and potentially complementary information for pCR prediction in TNBC. Citation Format: Shane Stecklein, S.R. Stecklein, M. Martín, G. Villacampa, M. Del Monte-Millán, R. Yoder, H. Pathak, S. Cobo, F. Brasó-Maristany, E.L. Álvarez, I. Echavarría, C. Bueno-Muiño, Y. Jerez, M. Cebollero, O. Bueno, J.Á. García-Saenz, F. Moreno, H. Gómez, T. Massarrah, B. Herrero, L. Paré, S. López-Tarruella, P. Villagrasa, A.K. Godwin, R. Salgado, A. Prat, P. Sharma. TNBC-DX Genomic Test Predicts High pCR in Triple-Negative Breast Cancer with sTILs ≥30% Treated with Neoadjuvant Docetaxel-Carboplatin with/without Pembrolizumab [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS4-10.