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. 2025 Apr 4;20:35. doi: 10.1186/s13000-025-01624-3

Table 2.

Inter-reader agreement for central pathologists with HER2-low training

HER2 IHC score cutoff OPA, % (95% CI) Fleiss’ kappa
Pathologists
1 vs. 2
Pathologists
2 vs. 3
Pathologists
1 vs. 3
0 absent membrane staininga, b vs. 0 with membrane staininga 1+, 2+, 3+ 96 (93–97) 96 (94–98) 97 (95–99) 0.68
0c vs. 1+, 2+, 3+ 94 (92–96) 94 (92–96) 91 (88–94) 0.79
0, 1 + vs. 2+, 3+ 85 (81–88) 85 (81–88) 94 (90–95) 0.74
0, 1+, 2 + vs. 3+ 97 (95–98) 87 (84–90) 87 (84–90) 0.67

CI: confidence interval; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; OPA: overall percent agreement

a “IHC 0 absent membrane staining” and “IHC 0 with membrane staining” are part of the IHC 0 score per American Society of Clinical Oncology/College of American Pathologists 2018 guidelines [2]

b Cutoff explored in DESTINY-Breast06 [17]

c Cutoff for HER2-low used in DESTINY-Breast04 [12]