Meredith C. Henderson, Michael Silver, Quynh Tran, Elias E. Letsios, Rao Mulpuri, David E. Reese, Ana P. Lourenco, Joshua LaBaer, Karen S. Anderson, Josie Alpers, Carrie Costantini, Nitin Rohatgi, Haythem Ali, Karen Baker, Donald W. Northfelt, Karthik Ghosh, Stephen R. Grobmyer, Winnie Polen, Judith K. Wolf

With improvements in breast cancer (BC) imaging, there has been a corresponding increase in false-positives and avoidable biopsies. There is a need to better differentiate when a breast biopsy is warranted and determine appropriate follow-up. This study describes the design and clinical performance of a combinatorial proteomic biomarker assay (CPBA), Videssa® Breast, in women over age 50. A BI-RADS 3, 4, or 5 assessment was required for clinical trial enrollment. Serum was collected prior to breast biopsy and subjects were followed for 6-12 months and clinically relevant outcomes recorded. Samples were split into training (70%) and validation (30%) cohorts with an approximate 1:4 case:control ratio in both arms. A CPBA that combines biomarker data with patient clinical data was developed using a training cohort (469 women, cancer incidence: 18.5%), resulting in 94% sensitivity and 97% negative predictive value (NPV). Independent validation of the final algorithm in 194 subjects (BC incidence: 19.6%) demonstrated a sensitivity of 95% and a NPV of 97%. When combined with previously published data for women under age 50, Videssa Breast achieves a comprehensive 93% sensitivity and 98% NPV in a population of women ages 25 - 75. Had Videssa Breast results been incorporated into the clinical workflow, approximately 45% of biopsies might have been avoided. Videssa Breast combines serum biomarkers with clinical patient characteristics to provide clinicians with additional information for patients with indeterminate breast imaging results, potentially reducing false-positive breast biopsies.