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Although circulating tumor cells (CTCs) have been studied in early breast cancer (EBC), their value in this setting is still not fully understood. We isolated and studied CTCs in the peripheral blood (PB) of 48 EBC patients pre-surgery and one and 6 months post-surgery using an approach involving EpCAM-independent enrichment and a dielectrophoresis-based device. Method feasibility and the correlation between CTCs and primary tumor features were evaluated. CTCs were found in 27.1% of pre-surgery patients, 20.9% of patients one-month post-surgery, and about 33% of patients 6-months post-surgery. CTCs were recovered singly for further molecular characterization. Pre-surgery CTC-positive patients more frequently had negative prognostic features, i.e. high proliferation, large tumor dimension, lymph node positivity and negative receptor status than the other subgroup. In particular, vascular invasion showed a statistically significant correlation with CTC-positivity. Our procedure proved feasible and capable of recovering CTCs from EBC patients. Furthermore, our results suggest that CTCs may be linked to vascular invasion and to other known negative prognostic factors.

The characterization of circulating tumor cells (CTCs) could substantially improve the management of cancer patients. However, their study is still a matter of debate, often due to lymphocyte contamination. In the present paper, an investigation of CTCs was carried out for the first time using DEPArray, a dielectrophoresis-based platform able to detect and sort pure CTCs. Analyses were conducted on peripheral blood (PB) samples from patients with metastatic colon cancer. After 100% pure cell recovery and whole genome amplification, KRAS gene mutation of CTCs was screened and compared to gene status in the primary tumor tissue. CTCs were found in 21 colon cancer patients (52.5%), with more than three tumor cells per 7.5 ml. KRAS gene mutation analysis, showed a mutational concordance between CTCs and primary tumor in 50% of matched cases. The present study demonstrates for the first time the feasibility of analyzing at the molecular level pure CTCs avoiding lymphocyte contamination using an innovative instrumentation, and a KRAS discordance between CTCs and primary tissue. Our results present dielectrophoresis-based procedures as a new standard in single cell analysis and recovery and invite careful reflection on the value of CTCs characterization.

Circulating tumor cells (CTCs) are cellular elements of undeniable significance that spread from the tumor mass into the peripheral blood and constitute one of the main vehicles for disease diffusion. Their rarity, in addition to a number of molecular and cellular features, has severely impaired research and exploitation. CTCs have been evaluated in early breast cancer (EBC), although long from being fully accepted in this field also due to a lack of technical standardization. CTCs hold promise to be a powerful non-invasive real-time measurable biomarker in all disease stages. This hypothesis is particularly appealing in the adjuvant setting of breast cancer, as it still lacks a marker that could play a central role in monitoring disease-free intervals, predicting early relapse and guiding drug selection. This review aimed to discuss CTC characteristics and show the main results of CTC-research in EBC setting, stating the urgency to continue basic and translational research in this field to definitely translate this marker from bench to bedside.