U.S. payer budget impact of using an AI-augmented cancer risk discrimination digital histopathology platform to identify high-risk of recurrence in women with early-stage invasive breast cancer.

AIMS: Use of gene expression signatures to predict adjuvant chemotherapy benefit in women with early-stage breast cancer is increasing. However, high cost, limited access, and eligibility for these tests results in the adoption of less precise assessment approaches. This study evaluates the cost impact of PreciseDx Breast (PDxBr), an AI-augmented histopathology platform that assesses the 6-year risk of recurrence in early-stage invasive breast cancer patients to help improve informed use of adjuvant chemotherapy. MATERIALS AND METHODS: A decision-tree Markov model was developed to compare the costs of treatment guided by standard of care (SOC) risk assessment (i.e. clinical diagnostic workup with or without Oncotype DX) versus PDxBr with SOC in a hypothetical cohort of U.S. women with early-stage invasive breast cancer. A commercial payer perspective compares costs of testing, adjuvant therapy, recurrence, adverse events, surveillance, and end-of-life care. RESULTS: PDxBr use in prognostic evaluation resulted in savings of $4 million (M) in year one compared to current SOC in 1 M females members. Over 6-years, savings increased to $12.5 M. The per-treated patient costs in year one amounted to $19.5 thousand (K) for SOC and $16.9K for PDxBr. LIMITATIONS: For simplicity, recurrence was not specified. We performed scenario analyses to account for variations in rates for local, regional, and distant recurrence. Second, a recurrent patient incurs the total cost of treated recurrence in the first year and goes back to remission or death. Third, CDK4/6i treatment is only incorporated in the recurrence costs but not in the first line of treatment for early-stage breast cancer due to limited data. CONCLUSIONS: Sensitivity analyses demonstrated robust overall savings to changes in all variables in the model. The use of PDxBr to assess breast cancer recurrence risk has the potential to fill gaps in care and reduce costs when gene expression signatures are not available.

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

BACKGROUND: PreciseDx Breast (PDxBr) 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's age, tumor size, stage, and lymph node status predict disease free survival using a proprietary algorithm. Here, analytical validation of the automated annotation process and extracted histologic digital features of the PDxBr 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 were 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.