Prognostic Significance of the CPS-EG Score in Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by substantial biological heterogeneity and variable clinical outcomes. Reliable prognostic tools are needed to improve risk stratification following neoadjuvant chemotherapy (NACT). This study aimed to evaluate the association of the Clinical–Pathologic Stage, Estrogen/Grade (CPS-EG) score with pathological complete response (pCR) and survival outcomes in patients with locally advanced TNBC treated with NACT. Methods: In this multicenter retrospective cohort study, 690 patients with locally advanced TNBC treated with NACT between 2010 and 2024 at 25 oncology centers were included. Patients were categorized according to CPS-EG score (≤3 vs. >3). Associations between CPS-EG score, clinicopathological characteristics, pCR, disease-free survival (DFS), and overall survival (OS) were analyzed. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses. Results: Patients with a CPS-EG score > 3 had significantly lower pCR rates and higher recurrence rates compared with those with a CPS-EG score ≤ 3 (p < 0.001 for both). Five-year OS rates were 83.7% and 54.1% in the CPS-EG ≤ 3 and > 3 groups, respectively, while the corresponding five-year DFS rates were 76.4% and 51.9% (p < 0.001 for both). In the multivariable analysis, CPS-EG > 3 remained independently associated with worse OS (HR 1.46, 95% CI 1.08–1.98, p = 0.015) and DFS (HR 1.73, 95% CI 1.26–2.38, p < 0.001). Conclusions: A higher CPS-EG score is associated with a lower likelihood of achieving pCR and poorer long-term survival outcomes in patients with locally advanced TNBC treated with NACT. The CPS-EG score represents a simple and readily available tool that may support risk stratification and clinical decision-making in routine practice.