Digital Pathology for HER2 Scoring in Breast Cancer: Concordance with Light Microscopy

Abstract

Introduction: HER2 status guides trastuzumab therapy in breast cancer. Digital pathology (whole-slide imaging, WSI) is increasingly used, but diagnostic concordance with light microscopy (LM) for HER2 immunohistochemistry (IHC) and in-situ hybridization (ISH) requires validation.
Methods: Systematic review of 10 studies (n=1,867 breast cancer cases) comparing WSI versus LM for HER2 IHC scoring (0, 1+, 2+, 3+) and ISH interpretation (ratio ≥2.0). Five pathologists per study, washout period ≥4 weeks. Primary outcome: intraclass correlation coefficient (ICC) for IHC, percent agreement for ISH.
Results: For IHC, ICC between WSI and LM was 0.91 (95% CI 0.88–0.94). Perfect agreement (same score) was 86% (83–89%). Discordant cases were mostly 1+ vs 2+ (8%) or 2+ vs 3+ (4%). For ISH, agreement was 98% (kappa 0.95). Pathologists reported less fatigue with WSI but longer reading time (+22%). Monitor resolution and color calibration affected interpretation in 5% of slides.
Discussion: WSI is non-inferior to LM for HER2 assessment when monitors are calibrated and resolution is adequate.
Conclusion: Digital pathology is acceptable for primary HER2 diagnosis in breast cancer with appropriate quality assurance.