PS4-05-10: Plasma neurofilament light chain levels are prognostic in patients with primary breast cancer and are associated with CTC

Abstract Background: Increased tumor innervation has been associated with more aggressive tumor behaviour and worse clinical outcomes across multiple cancer types. Emerging evidence suggests that heightened neural infiltration may lead to axonal damage. Neurofilaments (NfL), key structural components of neurons, have been proposed as biomarkers of neuronal damage, but their prognostic role in solid tumors remains unclear. This study aimed to assess the clinical significance of plasma neurofilament light chain levels in early-stage breast cancer. Methods: We prospectively analyzed plasma neurofilament light chain concentrations in 80 patients with non-metastatic breast cancer prior to systemic treatment that underwent surgery at National Cancer Institute, Slovakia from 2013 to 2015. NfL level was determined by ELISA. Associations with clinicopathological features and circulating tumor cells (CTCs) were evaluated using descriptive and inferential statistics. Survival outcomes were analyzed using Kaplan-Meier curves and log-rank tests, with a cut-off set higher than 95th percentile of the normative distribution. Results: NfL light chain levels were not significantly associated with tumor size, nodal status, histological grade, hormone receptor, HER2, or Ki-67 status. However, higher NfL levels were significantly associated with negative Bcl-2 expression (mean 13.1 vs. 9.2 ng/mL, p = 0.012). Moreover, patients with high NfL plasma level had detectable CTCs with epithelial-mesenchymal transition phenotype compared to patients with low NfL level (66.7% vs. 25.4%, p = 0.01). Patients with low plasma neurofilament levels had significantly improved disease-free survival (HR = 0.23, 95% CI 0.05–1.08, p = 0.0006) and overall survival (HR = 0.19, 95% CI 0.03–1.16, p = 0.0005) compared to those with high levels. Multivariate analysis confirmed prognostic value of NfL light chain levels independently of tumor stage, nodal status, oestrogen receptor and/or HER2 status. Conclusions: Plasma NfL light chain level concentration is a promising prognostic biomarker in non-metastatic breast cancer, independently of conventional pathological features. Its association with poor survival and CTC EMT phenotype suggests a potential link to tumor aggressiveness and dissemination potential. Citation Format: M. Mego, J. Hanes, V. Parrak, G. Minarik, M. Karaba, B. Mravec, P. Turcani, K. Kalavska, L. Kucerova, N. Zilka. Plasma neurofilament light chain levels are prognostic in patients with primary breast cancer and are associated with CTC [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 PS4-05-10.