HER2-positive circulating tumor cells in breast cancer.
OBJECTIVE
Circulating Tumor Cells (CTCs) detection and phenotyping are currently evaluated in Breast Cancer (BC). Tumor cell dissemination has been suggested to occur early in BC progression. To interrogate dissemination in BC, we studied CTCs and HER2 expression on CTCs across the spectrum of BC staging.


METHODS
Spiking experiments with 6 BC cell lines were performed and blood samples from healthy women and women with BC were analyzed for HER2-positive CTCs using the CellSearch®.


RESULTS
Based on BC cell lines experiments, HER2-positive CTCs were defined as CTCs with HER2 immunofluorescence intensity that was at least 2.5 times higher than the background. No HER2-positive CTC was detected in 42 women without BC (95% confidence interval (CI) 0-8.4%) whereas 4.1% (95%CI 1.4-11.4%) of 73 patients with ductal/lobular carcinoma in situ (DCIS/LCIS) had 1 HER2-positive CTC/22.5 mL, 7.9%, (95%CI 4.1-14.9%) of 101 women with non metastatic (M0) BC had ≥1 HER2-positive CTC/22.5 mL (median 1 cell, range 1-3 cells) and 35.9% (95%CI 22.7-51.9%) of 39 patients with metastatic BC had ≥1 HER2-positive CTC/7.5 mL (median 1.5 cells, range 1-42 cells). In CTC-positive women with DCIS/LCIS or M0 BC, HER2-positive CTCs were more commonly detected in HER2-positive (5 of 5 women) than HER2-negative BC (5 of 12 women) (p = 0.03).


CONCLUSIONS
HER2-positive CTCs were detected in DCIS/LCIS or M0 BC irrespective of the primary tumor HER2 status. Nevertheless, their presence was more common in women with HER2-positive disease. Monitoring of HER2 expression on CTCs might be useful in trials with anti-HER2 therapies.
Department of Medical Oncology, Institut Jules Bordet, Brussels, Belgium. Michail.Ignatiadis@bordet.be
Michail
M
Ignatiadis
Françoise
F
Rothé
Carole
C
Chaboteaux
Virginie
V
Durbecq
Ghizlane
G
Rouas
Carmen
C
Criscitiello
Jessica
J
Metallo
Naima
N
Kheddoumi
Sandeep K
SK
Singhal
Stefan
S
Michiels
Isabelle
I
Veys
José
J
Rossari
Denis
D
Larsimont
Birgit
B
Carly
Marta
M
Pestrin
Silvia
S
Bessi
Frédéric
F
Buxant
Fabienne
F
Liebens
Martine
M
Piccart
Christos
C
Sotiriou
D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000737:chemistry* / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
Clin Chem Lab Med. 2005;43(6):617-27
16006258
Clin Cancer Res. 2010 May 1;16(9):2634-45
20406831
Clin Cancer Res. 2004 Oct 15;10(20):6897-904
15501967
Ann Oncol. 2010 Apr;21(4):729-733
19850639
Breast Cancer Res. 2007;9(5):R74
17963511
Cancer Cell. 2008 Jan;13(1):58-68
18167340
Breast Cancer Res Treat. 2009 Feb;113(3):501-7
18327638
Clin Cancer Res. 2006 Mar 15;12(6):1715-20
16551854
Curr Opin Oncol. 2010 Nov;22(6):552-8
20706122
J Clin Oncol. 2007 Jan 1;25(1):118-45
17159189
Histopathology. 1991 Nov;19(5):403-10
1757079
Breast Cancer Res Treat. 2009 Dec;118(3):523-30
19597704
Nat Rev Cancer. 2008 May;8(5):329-40
18404148
N Engl J Med. 2004 Aug 19;351(8):781-91
15317891
Cytometry A. 2007 Mar;71(3):154-62
17200956
J Clin Oncol. 1999 May;17(5):1474-81
10334533
Int J Oncol. 2002 Nov;21(5):1111-7
12370762
Cancer Res. 2001 Mar 1;61(5):1890-5
11280743
J Clin Oncol. 2005 Dec 20;23(36):9067-72
16172462
J Clin Pathol. 2000 Aug;53(8):634-5
11002770
Proc Natl Acad Sci U S A. 2004 Jun 22;101(25):9393-8
15194824
Ann Surg Oncol. 2010 Jun;17(6):1539-45
20135356
Cytometry. 2001 Jan 1;43(1):31-7
11122482
Breast Cancer Res Treat. 2006 Jul;98(2):179-84
16552629
Clin Cancer Res. 2008 Nov 1;14(21):7004-10
18980996