Clinical performance of novel exosomal liquid RNA biopsy assay in breast cancer segment.

Abstract

e12561 Background: Exosomal RNA captures dynamic tumor biology and may overcome limitations of tissue biopsy and imaging, which, in the breast cancer segment, provide high false positivity and overdiagnosis (10-40%) and limitations with dense breast tissue with screening mammography and no reliable blood biomarkers for early recurrence or post-surgical risk stratification. A minimally invasive, real-time assay could improve detection and monitoring. Data suggest that gene expression signatures may predict indolent or aggressive breast cancer. CTOAM’s Liquid RNA (L-RNA) assay capitalizes on tumor-derived exosomal RNA. Unlike relatively static DNA, RNA expression dynamically reflects cellular and functional changes, providing real-time biological insights. Methods: CTOAM’s L-RNA assay uses AmpliSeq RNA NGS to quantify differentially expressed exosomal RNA in plasma relative to normal reference profiles. 35 retrospective cases were analyzed. Combined Positive Score (CPS) performance was compared with integrated clinical reference standards (biopsy and imaging) and with blood biomarkers alone. Results: Of 35 patients, 29 had breast cancer (19 HR +ve, 7 TNBC, 3 HER2+ve, stage 1 to 4), and 6 were true negatives. Compared with biopsy and imaging, the L-RNA assay demonstrated 100% sensitivity, 87.50% specificity, and 96.43% PPV, with an AUC of 93.80%. It identified molecular progression significantly earlier than imaging. CPS correlated with clinical tumor activity, ranging from 227 (low while on treatment) to 4035 (high), supporting its utility for early detection, treatment monitoring, and clarifying ambiguous imaging findings. Conclusions: CTOAM’s exosomal L-RNA assay demonstrates high diagnostic accuracy for early breast cancer detection, outperforming blood-based biomarkers alone and offering earlier insight than imaging modalities. As a minimally invasive adjunct to standard diagnostics, the assay has the potential to reduce unnecessary invasive procedures, resolve indeterminate imaging findings, and support longitudinal treatment monitoring. Larger prospective studies are needed to validate its clinical utility. L-RNA Efficacy data. Metric L-RNA vs Biopsy+Imaging (%) 95% CI L-RNA vs Blood biomarkers (%) 95% CI Sensitivity 100 (87.23-100.00) 88.89 (51.75-99.72) Specificity 87.50 (47.35-99.68) 75.00 (34.91-96.81) PPV (Precision) 96.43 (81.19-99.41) 80.00 (54.09-93.14) NPV 100 (59.04-100.00) 85.71 (47.53-97.55) Accuracy 97.14 (85.08-99.93) 82.35 (56.57-96.20) F1 Score 98.20 (92.00-99.60) 81.9 (61.00-93.00) ROC AUC 93.80 (78.50-98.90) 84.20 (60.00-95.00)