Diagnostic potential of serum BF-09 biomarker (protein SGF29) for early detection of breast cancer: high performance for early-stage cancer and major histological or molecular subtypes

Mammography is the standard-of-care for breast cancer (BCA) screening, albeit with significant issues related to tissue density and overdiagnosis of benign conditions leading to a growing interest in alternative blood-based tests. We previously characterized the BF-09 protein biomarker (SAGA-associated factor 29) as a circulating serum BCA antigen. In this feasibility study, we investigated its ability to discriminate between retrospectively collected BCA and non-cancer cases. The serum level of the BF-09 biomarker was measured by ELISA in 261 BCA and 136 controls (43 benign and 93 healthy cases) split between two independent sets. Diagnostic performance was evaluated in each set by receiver operating characteristics curves (ROC), to determine sensitivity (SE), specificity (SP), area under the curve (AUC), negative and positive predictive values. Additional internal validation was done via statistical resampling using bootstrapping and Monte Carlo cross-validation. Performance of the BF-09 biomarker in the training set (71 BCA patients and 56 controls) was characterized by an AUC of 0.92 (95% CI 0.86–0.96) with 87.3% SE at 85.7% SP using an optimal, Youden’s index selected cutoff (COF) point. In the validation set (190 BCA and 80 controls), the AUC was 0.95 (95%CI 0.91–0.97) with 93.2% SE at 85% SP using the fixed COF. Assay discriminatory power robustness was shown using statistical resampling. Assay performance remained steady across BCA stages, grades, histological subtypes, hormone receptor status and in women under 50. Our results suggest that BF-09 serum biomarker assay has high potential as an alternative blood-based screening test for BCA.