Analytical Validation of the PreciseDx Digital Prognostic Breast Cancer Test in Early-Stage Breast Cancer

Authors:
raw_author_name: Gerardo Fernandez
raw_affiliation_string: Icahn School of Medicine at Mount Sinai, New York, NY, US; PreciseDx, New York, NY, USA
raw_author_name: Jack Zeineh
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Marcel Prastawa
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Richard Scott
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Abishek Sainath Madduri
raw_affiliation_string: Icahn School of Medicine at Mount Sinai, New York, NY, US; PreciseDx, New York, NY, USA
raw_author_name: Alexander Shtabsky
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Shabnam Jaffer
raw_affiliation_string: Lenox Hill Hospital, New York, NY, US
raw_author_name: Aaron Feliz
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Brandon Veremis
raw_affiliation_string: Icahn School of Medicine at Mount Sinai, New York, NY, US; PreciseDx, New York, NY, USA
raw_author_name: Giovanni Koll
raw_affiliation_string: PreciseDx, New York, NY, USA
raw_author_name: Michael J. Donovan
raw_affiliation_string: Icahn School of Medicine at Mount Sinai, New York, NY, US; PreciseDx, New York, NY, USA; University of Miami, Pathology, Miami, FL, USA

Abstract: Background : PreciseDx Breast is a digital test that predicts early-stage breast cancer recurrence within 6-years of diagnosis. Materials and Methods : Using hematoxylin and eosin-stained whole slide images of invasive breast cancer (IBC) and artificial intelligence-enabled Morphology Feature Array, microanatomic features are generated. Morphometric attributes in combination with patient age, tumor size, stage and lymph node status predicts disease free survival using a proprietary algorithm. Here, analytical validation of the automated annotation process and extracted histologic digital features of the PreciseDx Breast test, including impact of methodologic variability on the composite risk score is presented. Studies of precision, repeatability, reproducibility and interference were performed on morphology feature array-derived features. The final risk score was assessed over 20-days with 2-operators, 2-runs/day and 2-replicates across 8-patients, allowing for calculation of within-run repeatability, between-run and within-laboratory reproducibility. Results : Analytical validation of features derived from whole slide images demonstrated a high-degree of precision for tumor segmentation (0.98, 0.98), lymphocyte detection (0.91, 0.93), and mitotic figures (0.85, 0.84). Correlation of variation of the assay risk score for both reproducibility and repeatability was less than 2%, and interference from variation in hematoxylin and eosin staining or tumor thickness was not observed demonstrating assay robustness across standard histopathology preparations. Conclusion : In summary, the analytical validation of the digital IBC risk assessment test demonstrated a strong performance across all features in the model and complimented the clinical validation of the assay previously shown to accurately predict recurrence within 6-years in early-stage invasive breast cancer patients. MicroAbstract: PreciseDx Breast (PDxBr) is a digital test, which generates an artificial-intelligent tumor grade and phenotype utilizing morphometric features derived from H&E images of invasive breast cancer to predict outcome. Analytical validation of the image analysis platform including robust accuracy of cell type identification and tissue architecture composition, combined with test reproducibility and reliability, is a critical requirement for approval and clinical adoption.