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Breast Cancer Research
Published in: Breast Cancer Research 3/2012

Open Access 01-06-2012 | Research article

Biomarkers characterization of circulating tumour cells in breast cancer patients

Authors: Rosa Nadal, Ana Fernandez, Pedro Sanchez-Rovira, Marta Salido, María Rodríguez, José Luis García-Puche, Marta Macià, Josep Maria Corominas, Miguel Delgado-Rodriguez, Lucas Gonzalez, Joan Albanell, Mónica Fernández, Francesc Solé, José Antonio Lorente, María José Serrano

Published in: Breast Cancer Research | Issue 3/2012

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Abstract

Introduction

Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease.

Methods

Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics.

Results

Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03).

Conclusions

This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted.
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Metadata
Title
Biomarkers characterization of circulating tumour cells in breast cancer patients
Authors
Rosa Nadal
Ana Fernandez
Pedro Sanchez-Rovira
Marta Salido
María Rodríguez
José Luis García-Puche
Marta Macià
Josep Maria Corominas
Miguel Delgado-Rodriguez
Lucas Gonzalez
Joan Albanell
Mónica Fernández
Francesc Solé
José Antonio Lorente
María José Serrano
Publication date
01-06-2012
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2012
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3180

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