Abstract PS1-03-04: Predictive Factors of Thyroid Adverse Events in Neoadjuvant Immunotherapy for Triple-Negative Breast Cancer

Abstract Background: Thyroid dysfunction is among the most common immune-related events (irAEs) of immune checkpoint inhibitors (ICIs). This study aimed to investigate the prevalence, risk factors, and prognostic implications of thyroid irAEs in triple-negative breast cancer (TNBC) patients receiving neoadjuvant anti-PD-1 therapy combined with chemotherapy, based on data from the TREND phase II prospective clinical trial. Methods: The TREND study is a phase II prospective clinical trial involving TNBC patients treated with tislelizumab combined with nab-paclitaxel, followed by epirubicin-cyclophosphamide before surgery. Data on demographics, thyroid function, anti-thyroid autoantibodies were collected, and univariate and multivariate logistic regression models were used to identify risk factors. Peripheral immune analysis and whole-exome sequencing were conducted to explore underlying mechanisms associated with thyroid irAEs. Results: Among the 50 patients analyzed, 14 (28%) developed thyroid irAEs. Multivariate analyses revealed that baseline positivity of thyroglobulin antibody (OR 9.311, p=0.011) and lower levels of free triiodothyronine levels (OR 0.056, p=0.034) are independent predictors of thyroid irAEs. Peripheral immune analysis revealed that patients with thyroid irAEs exhibited elevated levels of CD4+ T cells, CD8+ T cells and CD16+CD56+ NK cells, along with higher levels of CD4+T cells before the onset of thyroid irAEs. Additionally, increased tumor mutational burden, and mutations in KLF17 and LRIG1 were observed in patients with thyroid irAEs. Conclusions: This study highlights the risk factors and underlying pathogenesis associated with thyroid irAEs in TNBC patients treated with neoadjuvant anti-PD-1 therapy combined with chemotherapy. These findings may assist clinicians in identifying patients at elevated risk for irAEs during ICI therapy, thereby improving patient management in clinical practice. Citation Format: Y. Li, Y. Cheng, L. Ji, Y. Wang, L. Yao, H. Zhang, H. Dong, M. Wang, X. Yingying. Predictive Factors of Thyroid Adverse Events in Neoadjuvant Immunotherapy for 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 PS1-03-04.