Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative breast cancer survival
- Author(s)
- Wang, Y; Ter Hoeve, ND; Drubay, D; Pusztai, L; Jonas, SF; Dixon-Douglas, J; Acs, B; Adams, S; André, F; Badve, S; Bataillon, G; Carter, JM; Chia, S; Cockenpot, V; Colleoni, MA; Criscitiello, C; Curigliano, G; Dackus, GMHE; Demaria, S; Denkert, C; van Deurzen, CHM; Dieci, MV; Giardiello, D; Goetz, MP; Gray, RJ; Hauptmann, M; Jóźwiak, K; Koop, EA; de Jong, VMT; Joensuu, H; Jules-Clément, G; Kammler, R; Kellokumpu-Lehtinen, PL; Kim, SB; Kok, M; Lacroix-Triki, M; Lambertini, M; Lee, HJ; Lemonnier, J; Leon-Ferre, RA; Leung, S; Linderholm, B; Loibl, S; Martens, JWM; Nielsen, TO; Opdam, M; Pharoah, P; Penault-Llorca, F; Piccart, M; Riaz, N; Vincent-Salomon, A; Sparano, J; Shimoi, T; Sotiriou, C; Suman, VJ; Timmermans, AM; van Diest, PJ; Voogd, AC; Viale, G; Wolff, AC; Yazaki, S; Yoshida, M; Salgado, R; Linn, SC; Schmidt, MK; Loi, S; Michiels, S; International Immuno-Oncology Biomarker Working Group;
- Details
- Publication Year 2026-08,Volume 37,Issue #8,Page 1093-1105
- Journal Title
- Annals of Oncology
- Publication Type
- Research article
- Abstract
- BACKGROUND: Stromal tumor-infiltrating lymphocytes (sTILs) are a strong prognostic marker in patients with triple-negative breast cancer (TNBC). We aimed to incorporate sTILs into the PREDICT model for women with early-stage TNBC to guide chemotherapy decisions. PATIENTS AND METHODS: We included 3698 women with early-stage TNBC, diagnosed between 1979 and 2017, from two pooled cohorts with sTILs scored according to international guidelines to update PREDICT version 2.3. The updated model, PREDICT_sTILs, is a Cox regression model with sTILs and the PREDICT prognostic index as predictors and breast cancer-specific survival as the outcome. Internal-external validation was conducted using leave-one-region-out cross-validation, with calibration assessed by the observed-to-expected (O/E) ratio and discrimination by area under the curve (AUC). We compared the clinical values of PREDICT_sTILs and PREDICT through decision curve analysis, examining net true high-risk and low-risk classifications across risk thresholds of 10-year breast cancer mortality above 8%-15%. RESULTS: Among the 3698 patients, 1806 received chemotherapy while 1892 were chemotherapy-naïve. Chemotherapy-treated patients had a median age of 50 years, a tumor size of 25 mm, and one positive lymph node. The chemotherapy-naïve patients had a median age of 55 years, a tumor size of 20 mm, and 0 positive lymph nodes. Within 5 and 10 years, 741 and 860 deaths were attributed to breast cancer, respectively. PREDICT_sTILs showed strong internal-external validity, with comparable calibration and discrimination at both time points: pooled O/E ratios of 0.98 [95% confidence interval (CI) 0.69-1.41] at 5 years and 0.99 (95% CI 0.72-1.35) at 10 years, and AUCs of 0.74 (95% CI 0.72-0.77) and 0.74 (95% CI 0.70-0.78), respectively. Compared with PREDICT, PREDICT_sTILs identified 19-60 additional net true low-risk patients and 3-10 additional net true high-risk patients per 1000 chemotherapy-naïve patients at the risk thresholds of 8%-15% at 10 years. CONCLUSION: Adding sTILs to PREDICT improves its ability to inform chemotherapy decisions for early-stage patients with TNBC, especially in identifying low-risk individuals who may safely forgo chemotherapy.
- Publisher
- Elsevier
- Keywords
- Humans; *Triple Negative Breast Neoplasms/mortality/pathology/drug therapy/immunology; Female; *Lymphocytes, Tumor-Infiltrating/pathology/immunology; Prognosis; Middle Aged; Aged; Adult; Predict; chemotherapy-decision making; prognostication; triple-negative breast cancer; tumor-infiltrating lymphocytes
- Department(s)
- Laboratory Research; Medical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.annonc.2026.04.011
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-05-21 04:00:20
Last Modified: 2026-08-13 12:12:35