Abstract Introduction: Anxiety is a prevalent but often underrecognized comorbidity in breast cancer patients. Despite advances in systemic therapies that have improved the cure rates of early-stage disease, the psychological burden associated with diagnosis, treatment-related toxicity, and uncertainty about prognosis remains substantial. Emerging evidence suggests that anxiety may not only impair quality of life but also negatively impact treatment efficacy and survival. However, robust data on this association are lacking. This study represents the first large-scale, real-world investigation evaluating the impact of anxiety on pathological complete response (pCR) and disease-free survival (DFS) in early-stage breast cancer. The association between anxiety and pCR is reported here for the first time. Methods: In this single-center, real-world cohort study, 2,113 female patients with early-stage breast cancer treated between June 2023 and June 2025 were enrolled. Anxiety was assessed at baseline using the Zung Self-Rating Anxiety Scale (SAS), with scores ≥50 indicating clinically significant anxiety. Clinical and demographic data were collected, including tumor stage, treatment type, and reimbursement status. pCR was evaluated post-neoadjuvant therapy. DFS was defined as the interval from surgery to documented recurrence or last follow-up. Logistic regression and Cox proportional hazards models were used for multivariate analysis. Results: Of the 2,113 patients, 700 (33.1%) exhibited clinically significant anxiety, including 58 (8.3% of anxious patients) with severe anxiety. Higher anxiety prevalence was associated with age ≤50 years (P 0.001), more advanced tumor stage (P 0.001), and lower medical insurance coverage (P 0.05). BMI, marital status, and socioeconomic status were not significantly correlated. Patients with anxiety had significantly lower pCR rates (OR = 2.58; 95% CI: 1.82-3.71; P 0.001), a finding that remained significant after adjusting for potential confounders, including molecular subtype, tumor burden, and other clinical variables (adjusted OR = 2.83; 95% CI: 1.87-4.33; P 0.001). In survival analysis, the median DFS was 36.7 months in the anxiety group vs. 50.0 months in the non-anxiety group (P 0.001). Anxiety was an independent prognostic factor for inferior DFS in multivariate Cox regression (HR = 2.56; 95% CI: 1.51-4.32; P 0.001). Conclusion: This real-world study provides the first evidence that anxiety is an independent predictor of both lower pCR rates and shorter DFS in early-stage breast cancer. These findings underscore the clinical importance of routine psychological screening and timely intervention. Addressing anxiety may not only improve patient well-being but also enhance treatment response and survival outcomes. Citation Format: Y. Chen, J. Zhao, L. Ding, Q. Li, J. Chai, Y. Wang. First Real-World Evidence Linking Anxiety to Poorer Treatment Response and Survival in Early-Stage 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 PS2-04-04.
Chen et al. (Tue,) studied this question.