Hepcidin as an emerging predictor biomarker of leptomeningeal metastases in patients with metastatic breast cancer

Leptomeningeal metastatic disease (LMD) occurs in 5–19% of solid tumor cases, with breast cancer being a leading cause. Limited penetration of therapeutic agents into the CNS and increased patient survival may contribute to the rising incidence. Diagnosis relies on cerebrospinal fluid (CSF) cytology and MRI, but these have limited sensitivity, highlighting the need for improved biomarkers. In this exploratory study, we examined CSF and serum levels of NfL, GFAP, Tau, and Hepcidin in metastatic breast cancer patients with and without LM included in a prospective study, to evaluate their potential as biomarkers for LMD diagnosis, prognosis, and treatment decision-making. A total of 49 adult patients were included, among which 18 patients (LMD + group) had confirmed LMD based on CSF cytology and 31 were not confirmed as having LMD (LMD- group). In CSF, median concentrations of Hepcidin were 0.3 ng/mL and 1.4 ng/mL in LMD- and LMD + patients, respectively (p < 0.01). Using ROC analysis, the AUC yielded by CSF biomarkers to detect LMD was 0.909 for Hepcidin, 0.841 for proteinorachy, 0.722 for both NfL and GFAP and 0.703 for t-Tau (p < 0.05). The AUC yielded by serum Hepcidin to detect LMD was 0.514. Our findings indicate that CSF Hepcidin exhibits strong diagnostic potential for LMD detection, which could help clinicians in the early identification of this condition.