Prospective real time clinical validation of a novel circulating tumor–derived blood mRNA Geneverify test for diagnosis of breast cancer.

Abstract

e15053 Background: Early detection is critical for the effective management of breast cancer. We performed a real-time clinical validation of the plasma cell-free mRNA–based Geneverify test for early breast cancer screening and detection. This next-generation, minimally invasive assay offers rapid and precise molecular insights, with the potential to transform current diagnostic practices by reducing reliance on surgical biopsies. Methods: We evaluated the real-time expression of 30 different breast cancer associated genes in plasma samples collected from 57 subjects (39 cancer cases, 8 benign/ high risk subjects and 10 controls). Eligible participants were selected based on the availability of paired blood and surgical tissue specimens from cases suspected of breast cancer. We validated the diagnostic and prognostic potential of a multi-gene expression panel developed by Geneverify Inc. The log₂-fold change in gene expression was calculated to generate a risk score for each subject. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves and calibration analysis. Risk scores were compared against biopsy-confirmed diagnoses to calculate sensitivity and specificity. Geneverify scores were evaluated with respect to the patient’s stage, grade, and metastasis. Results: The Geneverify risk score effectively distinguished breast cancer patients from benign controls, demonstrating strong diagnostic discrimination with the ROC curve (AUC: 0.92, P < 0.001, 95% CI = 0.82 – 1.00). Using Youden’s Index a risk score cutoff of 17, the test achieved 100% sensitivity and 75% specificity for breast cancer detection. Spearman’s rank correlation demonstrated a significant positive association between Geneverify Dx scores and both clinical stage and pathological grade. Additionally, patients with metastatic disease exhibited higher risk scores compared with non-metastatic cases. Healthy controls and benign subjects showed markedly reduced gene expression levels and consistently low risk scores. Conclusions: This prospective study represents the first real-time clinical validation of a blood-based, cell-free mRNA Geneverify test for breast cancer. The assay demonstrated high diagnostic accuracy, a strong correlation with breast cancer presence and severity, and the potential to reduce dependence on invasive tissue biopsies. These results support the Geneverify test as a promising tool for early detection, risk stratification, and improved patient management in breast cancer.