Provista 002 prospective randomized trial utilizing Videssa in conjunction with imaging to detect breast cancer from patients with imaging findings age 25-75.

Abstract

31 Background: An approach to detection that relies on biochemical markers of breast cancer would significantly contribute to more accurate detection in women with suspicious lesions. The combination of imaging, which identifies anatomical anomalies consistent with cancer with proteomic approaches promises to provide a powerful detection paradigm. A proteomic detection approach would provide a powerful tool for the detection of breast cancer in women with dense breast, a diagnosis that is difficult utilizing imaging alone. While protein signatures for the presence of breast cancer have remained elusive, we have developed a novel approach that combines serum protein biomarkers with tumor-associated autoantibodies. We utilized prospectively collected serum samples to develop novel algorithms for use in conjunction with imaging. We tested whether the assay was able to distinguish benign from invasive breast cancers in a prospective, randomized setting. Methods: Provista-002 enrolled 509 patients from multiple sites across the US and followed for 6 months after the first blood draw under IRB approval. Patients were consented after assessment of a BIRADS 3 or 4 and considered eligible if they were between 25 and 75 years of age, no history of cancer, no prior breast biopsy within the last six months, and were assessed as BIRADS 3 or 4 within 28 days. Upon enrollment, patients were randomized to either training or validation groups. Clinical truth was considered equal to or greater than 80% sensitivity and/or specificity. Serum protein biomarkers and tumor-associated autoantibodies identified in prior proteomic screens were measured prior to biopsy in a blinded and randomized fashion. Individual biomarker concentrations, together with specific patient data were evaluated using various logistic regression models developed from prior studies. Results: Provista-002 demonstrated a clear difference between women under the age of 50 from over the age of 50 in both markers required for early detection and the algorithm (models) used to distinguish benign from invasive breast cancer/DCIS. This is the first study that demonstrates clearly that modeling of proteomic patterns differs significantly in the BIRADS 3/4 setting and in the detection of early breast cancer lesions. As demonstrated in Provista – 001, we did not observe a statistical difference between early detection in women with dense breast and those with mostly fatty breast. The ability of the Videssa assay to distinguish between invasive breast cancer/DCIS from benign breast conditions was demonstrated as 85.7% sensitivity and 82.4% specificity for women under the age of 50 (although, unfortunately all lesions were pathologically confirmed to be CIS) and in women over the age of 50, the sensitivity was 86.4% and specificity was 83%. Conclusions: As above, both age groups of women needed distinct marker sets and linear regressions to distinguish benign (non-clinically significant) lesions from those that needed further evaluation (DCIS and IBC). Clinical trial information: NCT02078570.