TY - JOUR
T1 - HER2-positive circulating tumor cells in breast cancer
AU - Ignatiadis, Michail
AU - Rothé, Françoise
AU - Chaboteaux, Carole
AU - Durbecq, Virginie
AU - Rouas, Ghizlane
AU - Criscitiello, Carmen
AU - Metallo, Jessica
AU - Kheddoumi, Naima
AU - Singhal, Sandeep K.
AU - Michiels, Stefan
AU - Veys, Isabelle
AU - Rossari, José
AU - Larsimont, Denis
AU - Carly, Birgit
AU - Pestrin, Marta
AU - Bessi, Silvia
AU - Buxant, Frédéric
AU - Liebens, Fabienne
AU - Piccart, Martine
AU - Sotiriou, Christos
PY - 2011/2/1
Y1 - 2011/2/1
N2 - Purpose: 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 immunofluoresence 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). Conclusion: 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.
AB - Purpose: 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 immunofluoresence 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). Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=79251548904&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0015624
DO - 10.1371/journal.pone.0015624
M3 - Article
C2 - 21264346
AN - SCOPUS:79251548904
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e15624
ER -