Abstract
In patients with metastatic breast cancer (MBC), brain metastases (BM) are associated with high morbidity and mortality. However, there is no validated serum biomarker that accurately predicts BM occurrence in these patients, and the role of serum biomarkers for prognosis remains unclear. Here, we evaluated the association of neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP) and tau serum levels with BM presence and prognosis in patients with MBC. In serum samples from patients with MBC with (n = 100) and without BM (n = 47), we measured the biomarker serum levels using single molecule array (Simoa) technology (Neurology-4-Plex assay). To evaluate their accuracy to identify patients with BM, we determined the receiver operating characteristic curve and the area under the curve (AUC) for each biomarker and calculated their sensitivity and specificity. The median serum levels of NfL, UCHL1, tau and GFAP were significantly higher in patients with BM. The AUC for GFAP (0.82, 95% confidence interval [CI] 0.75-0.88) was significantly higher than those of the other biomarkers considered independently. Using the medians as cutoff values, elevated serum levels of NfL, UCHL1, tau and GFAP were associated with BM in univariate analysis, but only high GFAP levels in multivariate analysis (odd ratio 23.4, 95% CI 6.8-80.5, P < .001). Elevated serum GFAP levels were independently associated with poor outcome. GFAP outperforms NfL, UCHL1 and tau as diagnostic and prognostic factor of BM in patients with MBC. These results must now be validated in an independent cohort of patients.