Journal
ANNALS OF ONCOLOGY
Volume 24, Issue 5, Pages 1231-1238Publisher
ELSEVIER
DOI: 10.1093/annonc/mds625
Keywords
automated analysis; breast cancer; circulating tumor cells; Her-2; quantitative assessment
Categories
Funding
- Veridex
- INCA DHOS [INCa-DHOS transla09-059]
- French government [PHRC AOM06156]
- Roche (Neuilly sur Seine, France)
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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 (R) 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.
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