HER2-positive circulating tumor cells in breast cancer

Michail Ignatiadis, Françoise Rothé, Carole Chaboteaux, Virginie Durbecq, Ghizlane Rouas, Carmen Criscitiello, Jessica Metallo, Naima Kheddoumi, Sandeep K. Singhal, Stefan Michiels, Isabelle Veys, José Rossari, Denis Larsimont, Birgit Carly, Marta Pestrin, Silvia Bessi, Frédéric Buxant, Fabienne Liebens, Martine Piccart, Christos Sotiriou

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Abstract

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.

Original languageEnglish
Article numbere15624
JournalPLoS One
Volume6
Issue number1
DOIs
Publication statusPublished - 2011

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Circulating Neoplastic Cells
breast neoplasms
Tumors
Cells
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
confidence interval
Confidence Intervals
neoplasm cells
Cell Line
cell lines
cells
Neoplasm Staging

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ignatiadis, M., Rothé, F., Chaboteaux, C., Durbecq, V., Rouas, G., Criscitiello, C., ... Sotiriou, C. (2011). HER2-positive circulating tumor cells in breast cancer. PLoS One, 6(1), [e15624]. https://doi.org/10.1371/journal.pone.0015624

HER2-positive circulating tumor cells in breast cancer. / Ignatiadis, Michail; Rothé, Françoise; Chaboteaux, Carole; Durbecq, Virginie; Rouas, Ghizlane; Criscitiello, Carmen; Metallo, Jessica; Kheddoumi, Naima; Singhal, Sandeep K.; Michiels, Stefan; Veys, Isabelle; Rossari, José; Larsimont, Denis; Carly, Birgit; Pestrin, Marta; Bessi, Silvia; Buxant, Frédéric; Liebens, Fabienne; Piccart, Martine; Sotiriou, Christos.

In: PLoS One, Vol. 6, No. 1, e15624, 2011.

Research output: Contribution to journalArticle

Ignatiadis, M, Rothé, F, Chaboteaux, C, Durbecq, V, Rouas, G, Criscitiello, C, Metallo, J, Kheddoumi, N, Singhal, SK, Michiels, S, Veys, I, Rossari, J, Larsimont, D, Carly, B, Pestrin, M, Bessi, S, Buxant, F, Liebens, F, Piccart, M & Sotiriou, C 2011, 'HER2-positive circulating tumor cells in breast cancer', PLoS One, vol. 6, no. 1, e15624. https://doi.org/10.1371/journal.pone.0015624
Ignatiadis M, Rothé F, Chaboteaux C, Durbecq V, Rouas G, Criscitiello C et al. HER2-positive circulating tumor cells in breast cancer. PLoS One. 2011;6(1). e15624. https://doi.org/10.1371/journal.pone.0015624
Ignatiadis, Michail ; Rothé, Françoise ; Chaboteaux, Carole ; Durbecq, Virginie ; Rouas, Ghizlane ; Criscitiello, Carmen ; Metallo, Jessica ; Kheddoumi, Naima ; Singhal, Sandeep K. ; Michiels, Stefan ; Veys, Isabelle ; Rossari, José ; Larsimont, Denis ; Carly, Birgit ; Pestrin, Marta ; Bessi, Silvia ; Buxant, Frédéric ; Liebens, Fabienne ; Piccart, Martine ; Sotiriou, Christos. / HER2-positive circulating tumor cells in breast cancer. In: PLoS One. 2011 ; Vol. 6, No. 1.
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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

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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.

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