Table 2.

HER2 expression on circulating tumor cells and primary breast cancer

				HER2+ CTCs/total CTCs (%)
Stage	HER2 PT	Enrichment/detection; CTC positive; CTC HER2 positive	CTC detection rate	HER2- PT	HER2+ PT	Reference
M0 and M1	FISH	EpCAM+ enrichment, C11, anti-CD45 (Her 81) HER2 CTC: IF, 0, 1+, 2+, 3+, FISH HER2+ CTCs: IF (3+), FISH HER2/CEP17 ≥2.0	NA	9/24 (37%)	11 of 15 (73%)	[74]
M0	IHC, FISH	Ficoll, immunomagnetic separation ICC CK, HER2 (21N clone) ≥1 HER2+ CTC/50 ml	17/35 (49%)	12/24 (50%)	2/3 (67%)	[75]
M0	IHC, FISH	CellSearch® ≥1 CTC/7.5 ml ≥1 HER2 (3+) CTC/7.5 ml (HER2 IF: 0, 1+, 2+, 3+)	Before NAC: 46/213 (22%) After NAC: 22/107 (11%)	8/37 (21%)	6/21 (28%)	[55]
IS and M0	IHC, FISH	CellSearch® ≥1 CTC/22.5 ml ≥1 HER2+ CTC/22.5 ml HER2 Intensity CellSearch® ≥ 2.5	IS: 6/73 (8%) M0:12/101(12%)	5/12 (41%)	5/5 (100%)	[59]
M0 and M1	IHC, FISH, CISH	CellSearch® ≥2 CTCs/7.5ml ≥50%HER2+ CTCs (HER2 IF: -, +)	40/66 (61%)	8/28 (29%)	7/12 (58%)	[76]
M1	IHC, FISH	AdnaTest®, RT-PCR	22/42 (52%)	5/17 (29%)	2/5 (40%)	[66]
M1	IHC, FISH	AdnaTest®, RT-PCR CellSearch® ≥5 CTCs/7.5 ml ≥1 HER2 (3+) CTC/7.5 ml (HER2 IF: 0, 1+, 2+, 3+)	90/229 (30%) 122/245 (50%)	28/57 (49%) 25/76 (33%)	9/22 (41%) 18/31 (58%)	[42]
M1	IHC, FISH,	CellSearch® ≥1 CTC/7.5 ml ≥1 HER2+ CTC/7.5 ml (HER2 IF: -, +)	57/76 (75%)	6/42 (14%)	13/15 (87%)	[77]
M1	IHC, FISH	CellSearch® Profiling Kit, FISH for HER2 ≥1 CTC/7.5 ml HER2+ CTCs: FISH HER2/CEP17 ≥2.0	75/75 (100%)	10/30 (33%)	44/45 (98%)	[78]
M1	IHC, FISH	CellSearch® ≥1 CTC/7.5 ml HER2 IF: 0, 1+, 2+, 3+ H-score ≥200 for HER2 IF	29/38 (76%)	3/18 (16%)	9/11 (82%)	[33]

CISH, chromogenic in situ hybridization; CTC, circulating tumor cell; EpCAM, epithelial cell adhesion molecule; FISH, fluorescent in situ hybridization; ICC, immunocytochemistry; IF, immunofluoresence; IHC, immunohistochemistry; IS, ductal/lobular carcinoma in situ; M0, non-metastatic; M1, metastatic; NA, not available; NAC, neoadjuvant chemotherapy; PT, primary tumor; RT-PCR, reverse transcription PCR.