. Author manuscript; available in PMC: 2013 Jul 8.

Published in final edited form as: Nat Rev Clin Oncol. 2011 Dec 6;9(1):48–57. doi: 10.1038/nrclinonc.2011.178

Table 3.

Reproducibility data of currently used biomarkers in breast cancer

Level of agreement	Type of test	Identical protocols (inter-laboratory and/or inter-observer)	Different protocols or technologies (inter-method)
Level 1 (κ ≥0.81) Almost perfect agreement	Pathology test	ER IHC testing, same antibody (+ vs −)^64–70 HER2 FISH testing (+ vs −)^71–76 HER2 IHC testing, same antibody (+ vs −)^65,77–79	NA
Level 1 (κ ≥0.81) Almost perfect agreement	Gene-expression-based test	Oncotype DX® and MammaPrint®^8,56,57 Basal-like and HER2E subtypes by supervised HC using different (microarray-based) intrinsic gene lists⁶²	Basal-like by different gene list and microarray platform intrinsic subtype centroid predictors (microarray-based)^63,107–109
Level 2 (κ 0.60–0.80) Substantial agreement	Pathology test	HER2 IHC testing, same antibody (+ vs −)^71,73,76,79 Histological grade^92,94,99 PR IHC testing (+ vs −)^65,66 ER IHC, 3 or more groups⁶⁴	ER IHC by different antibodies^69,85,87 ER by IHC vs LBA^{64,69,84–86} HER2 IHC by different antibodies^{104,115–117} HER2 by IHC vs FISH^77,101–104
Level 2 (κ 0.60–0.80) Substantial agreement	Gene-expression-based test	Overall intrinsic molecular subtypes identied by supervised HC using different intrinsic gene lists (microarray-based)⁶² Luminal A/luminal B/normal-like identied by supervised HC using different intrinsic gene lists (microarray-based)⁶²	Overall intrinsic molecular subtypes by different gene list and microarray platform intrinsic subtype centroid predictors^63,107–109
Level 3 (κ 0.40–0.59) Moderate agreement	Pathology test	Histological grade^91–98 ER IHC with 4 or more groups^64,67,90 PR IHC with 4 or more groups⁹⁰	PR by IHC vs LBA⁸⁴ PR IHC by different antibodies^68,87,118 ER IHC by different antibodies^72,118 HER2 by IHC/FISH vs FISH⁷²
Level 3 (κ 0.40–0.59) Moderate agreement	Gene-expression-based test	NA	Risk category groups^* comparing Oncotype DX® vs MammaPrint® and Oncotype DX® vs PAM50-ROR Overall intrinsic molecular subtypes by different gene list and microarray platform intrinsic subtype centroid predictors^63,107–109 HER2E/luminal A/luminal B/normal-like by different gene list and microarray platform intrinsic subtype centroid predictors (microarray-based)^63,107–109

All risk category groups have been calculated in the NKI295 dataset.¹⁵ For κ value calculation, low and intermediate groups of Oncotype DX® have been combined into a low-risk group when compared with two risk groups from MammaPrint®. For intrinsic molecular subtyping, a higher level of concordance is achieved when performing microarray platform to platform normalization, which was not performed by Weigelt et al.⁶³

Abbreviations: ER, estrogen receptor; FISH, fluorescence in situ hybridization; HC, hierarchical clustering; HER2E, HER2-enriched; IHC, immunohistochemistry; LBA, ligand-binding assay; NA, not applicable; PR, progesterone receptor.