Validation of an AI-based solution for breast cancer risk stratification using routine digital histopathology images

Background Stratipath Breast is a CE-IVD marked artificial intelligence-based solution for prognostic risk stratification of breast cancer patients into high- and low-risk groups, using haematoxylin and eosin (H&E)-stained histopathology whole slide images (WSIs). In this validation study, we assessed the prognostic performance of Stratipath Breast in two independent breast cancer cohorts. Methods This retrospective multi-site validation study included 2719 patients with primary breast cancer from two Swedish hospitals. The Stratipath Breast tool was applied to stratify patients based on digitised WSIs of the diagnostic H&E-stained tissue sections from surgically resected tumours. The prognostic performance was evaluated using time-to-event analysis by multivariable Cox Proportional Hazards analysis with progression-free survival (PFS) as the primary endpoint. Results In the clinically relevant oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative patient subgroup, the estimated hazard ratio (HR) associated with PFS between low- and high-risk groups was 2.76 (95% CI: 1.63-4.66, p-value < 0.001) after adjusting for established risk factors. In the ER+/HER2-Nottingham histological grade (NHG) 2 subgroup, the HR was 2.20 (95% CI: 1.22-3.98, p-value = 0.009) between low- and high-risk groups. Conclusion The results indicate an independent prognostic value of Stratipath Breast among all breast cancer patients, as well as in the clinically relevant ER+/HER2-subgroup and the NHG2/ER+/HER2-subgroup. Improved risk stratification of intermediate-risk ER+/HER2-breast cancers provides information relevant for treatment decisions of adjuvant chemotherapy and has the potential to reduce both under- and overtreatment. Image-based risk stratification provides the added benefit of short lead times and substantially lower cost compared to molecular diagnostics and therefore has the potential to reach broader patient groups.