Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer

S.T. Ligthart; F.-C. Bidard; C. Decraene; T. Bachelot; S. Delaloge; E. Brain; M. Campone; P. Viens; J.-Y. Pierga; L.W.M.M. Terstappen

doi:10.1093/annonc/mds625

Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer

S.T. Ligthart, F.-C. Bidard, C. Decraene, T. Bachelot, S. Delaloge, E. Brain, M. Campone, P. Viens, J.-Y. Pierga, L.W.M.M. Terstappen^*

^*Corresponding author for this work

Medical Cell Biophysics

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Abstract

Background: Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs.

Patients and methods: Her-2 assessment of CTCs was carried out using the CellSearch^® system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2-fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample.

Results: Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients.

Conclusions: Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.

Original language	English
Pages (from-to)	1231-1238
Number of pages	8
Journal	Annals of oncology
Volume	24
Issue number	5
DOIs	https://doi.org/10.1093/annonc/mds625
Publication status	Published - May 2013

Keywords

Automated analysis
Breast cancer
Circulating tumor cells
Her-2
Quantitative assessment
n/a OA procedure

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ligthart, S. T., Bidard, F.-C., Decraene, C., Bachelot, T., Delaloge, S., Brain, E., Campone, M., Viens, P., Pierga, J.-Y., & Terstappen, L. W. M. M. (2013). Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer. Annals of oncology, 24(5), 1231-1238. https://doi.org/10.1093/annonc/mds625

@article{51b2fe8ccdc342d9b5ec933fbccbbc2e,

title = "Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer",

abstract = "Background: Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs.Patients and methods: Her-2 assessment of CTCs was carried out using the CellSearch{\textregistered} system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2-fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample.Results: Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients.Conclusions: Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.",

keywords = "Automated analysis, Breast cancer, Circulating tumor cells, Her-2, Quantitative assessment, n/a OA procedure",

author = "S.T. Ligthart and F.-C. Bidard and C. Decraene and T. Bachelot and S. Delaloge and E. Brain and M. Campone and P. Viens and J.-Y. Pierga and L.W.M.M. Terstappen",

note = "Funding Information: This work was supported by Veridex and INCA DHOS [INCa-DHOS transla09-059]. The IC 2006-04 study was funded by a public grant from the French government [PHRC AOM06156]. The Beverly 01 and 02 studies were funded by Roche (Neuilly sur Seine, France). The sponsors of the study had no role in the study{\textquoteright}s design, data analysis, data interpretation or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication.",

year = "2013",

month = may,

doi = "10.1093/annonc/mds625",

language = "English",

volume = "24",

pages = "1231--1238",

journal = "Annals of oncology",

issn = "0923-7534",

publisher = "Elsevier Ltd",

number = "5",

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TY - JOUR

T1 - Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer

AU - Ligthart, S.T.

AU - Bidard, F.-C.

AU - Decraene, C.

AU - Bachelot, T.

AU - Delaloge, S.

AU - Brain, E.

AU - Campone, M.

AU - Viens, P.

AU - Pierga, J.-Y.

AU - Terstappen, L.W.M.M.

N1 - Funding Information: This work was supported by Veridex and INCA DHOS [INCa-DHOS transla09-059]. The IC 2006-04 study was funded by a public grant from the French government [PHRC AOM06156]. The Beverly 01 and 02 studies were funded by Roche (Neuilly sur Seine, France). The sponsors of the study had no role in the study’s design, data analysis, data interpretation or writing of the report. All authors had full access to all the data and the corresponding author had final responsibility for the decision to submit for publication.

PY - 2013/5

Y1 - 2013/5

N2 - Background: Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs.Patients and methods: Her-2 assessment of CTCs was carried out using the CellSearch® system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2-fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample.Results: Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients.Conclusions: Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.

AB - Background: Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs.Patients and methods: Her-2 assessment of CTCs was carried out using the CellSearch® system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2-fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample.Results: Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients.Conclusions: Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.

KW - Automated analysis

KW - Breast cancer

KW - Circulating tumor cells

KW - Her-2

KW - Quantitative assessment

KW - n/a OA procedure

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U2 - 10.1093/annonc/mds625

DO - 10.1093/annonc/mds625

M3 - Article

C2 - 23275633

SN - 0923-7534

VL - 24

SP - 1231

EP - 1238

JO - Annals of oncology

JF - Annals of oncology

IS - 5

ER -

Unbiased quantitative assessment of Her-2 expression of circulating tumor cells in patients with metastatic and non-metastatic breast cancer

Abstract

Keywords

UN SDGs

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