Biomarkers Characterization of Circulating Tumour Cells in Breast Cancer Patients
Menée sur 98 patientes atteintes d'un cancer non métastatique du sein, cette étude évalue la faisabilité de mesurer des biomarqueurs dans les cellules tumorales circulantes pour orienter le choix thérapeutique et assurer le suivi du traitement
INTRODUCTION:Increasing evidence supports that the detection of circulating tumour cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumour 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:98 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 CTCs 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 with clinical-pathological characteristics.RESULTS:Baseline detection rate was 46.9% [greater than or equal to]1 CTC/30 ml threshold. CTCs-positive were more frequent in HER2-negative tumours (p=0.046). In patients younger than 50 years old, HER2 amplified and G1-G2 tumours had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HR) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumour were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated to Luminal tumours (p=0.03).CONCLUSION:This is the largest exploratory CTCs biomarker analysis in nonmetastatic BC patients. Our study suggests that CTCs biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarkers 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 tumours is warranted.
Breast Cancer Research , article en libre accès, 2011