Quantitative measurement of HER2 expression in breast cancers: comparison with ‘real-world’ routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival

Table 2 Concordance of HERmark with local HER2 IHC, central HER2 IHC, local HER2 FISH, and local clinical HER2 status

			Local HER2 IHC								Central HER2 IHC								Local HER2 FISH								Local clinical HER2 status
			Negative		Equivocal		Positive		Total IHC		Negative		Equivocal		Positive		Total IHC		Non-amplified		Amplified		Total FISH		Negative		Equivocal		Positive		Total HER2
			N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%	N	%
HERmark	Negative		69	71%	14	14%	14	14%	97	51%	86	86%	13	13%	1	1%	100	52%	27	90%	3	10%	30	45%	83	83%	1	1%	16	16%	100	52%
HERmark	Equivocal		10	38%	9	35%	7	27%	26	14%	17	71%	5	21%	2	8%	24	13%	11	92%	1	8%	12	18%	17	65%	0	0%	9	35%	26	13%
HERmark	Positive		9	13%	7	10%	52	76%	68	36%	4	6%	23	34%	41	60%	68	35%	5	20%	20	80%	25	37%	10	15%	0	0%	58	85%	68	35%
		Total	88	46%	30	16%	73	38%	191	100%	107	56%	41	21%	44	23%	192	100%	43	64%	24	36%	67	100%	110	57%	1	1%	83	43%	194	100%
Overall concordance			68%, (69 + 9 + 52)/191								69%, (86 + 5 + 41)/192								NA^#						73%, (83 + 0 + 58)/194
Kappa (CI 95%), overall			0.475 (0.373 to 0.578); weighted Kappa = 0.545								0.481 (0.386 to 0.576); weighted Kappa = 0.631														0.510 (0.409 to 0.610); weighted Kappa = 0.583
Concordance, excluding Eqv.^*			84%, (69 + 52)/(69 + 9 + 14 + 52)								96%, (86 + 41)/(86 + 4 + 1 + 41)								85%, (27 + 20)/(27 + 5 + 3 + 20)						84%, (83 + 58)/(83 + 10 + 16 + 58)
Kappa (CI 95%), excluding Eqv.			0.676 (0.550 to 0.797)								0.914 (0.841 to 0.988)								0.705 (0.516 to 0.893)						0.682 (0.570 to 0.794)

^*Equivocal (Eqv.) cases from both tests were excluded; ^#NA, overall concordance was not calculated for 2 x 3 table. Central HER2 IHC retesting was performed retrospectively and central HER2 status was defined per ASCO/CAP guidelines for HER2 testing [7]. The results of local HER2 testing were reported by participating study sites based on local IHC and/or local FISH. Percentages may not add up to 100% due to rounding. CI, confidence interval; FISH, fluorescence in situ hybridization; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry.

ISSN: 1465-542X