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(®) 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.
authors.affiliation: Medical Cell BioPhysics Group, University of Twente, Enschede, The Netherlands.
authors.forename: S T
authors.initials: ST
authors.lastname: Ligthart
authors.forename: F-C
authors.initials: FC
authors.lastname: Bidard
authors.forename: C
authors.initials: C
authors.lastname: Decraene
authors.forename: T
authors.initials: T
authors.lastname: Bachelot
authors.forename: S
authors.initials: S
authors.lastname: Delaloge
authors.forename: E
authors.initials: E
authors.lastname: Brain
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.forename: J-Y
authors.initials: JY
authors.lastname: Pierga
authors.forename: L W M M
authors.initials: LW
authors.lastname: Terstappen
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human