Serum Proteomic Profiling by SomaScan Aptamer Array Identifies Candidate Predictive and Monitoring Biomarkers of Distant Recurrence in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) lacks a blood-based biomarker for predicting or monitoring distant recurrence. We profiled 39 serum samples from 38 women (10 healthy controls; 12 non-recurrent [NR]; eight diagnosis-timepoint samples from patients who later recurred [DR-DIG]; nine recurrence-timepoint samples [DR-REC]) using the SomaScan v5.0 aptamer platform). Public tumor-tissue transcriptomic cohorts were used for supportive and exploratory analyses. No protein reached a false discovery rate (FDR) < 0.05 for NR vs. DR-DIG; granzyme A (GZMA) and endoplasmic reticulum aminopeptidase 1 (ERAP1) showed the strongest nominal signals. For DR-DIG vs. DR-REC, 38 aptamers (37 proteins) reached FDR < 0.05, enriched for RNA-binding and nuclear-envelope proteins; this signature was retained in leave-one-out and storage-adjusted analyses. Higher GZMA mRNA was associated with longer recurrence-free survival in two independent cohorts (hazard ratio [HR] = 0.795, p = 0.018; HR = 0.186, p = 0.0057). Monitor genes showed near-chance concordance with metastatic tissue, and the source of the signature could not be resolved. An exploratory four-gene elastic-net panel reached a concordance index of 0.613 internally but 0.559 externally. GZMA is a candidate serum biomarker of TNBC recurrence risk, and the monitor signature is a preliminary observation. Both require protein-level validation in independent, prospectively collected serum cohorts.