Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study

Georgoulias, Vasilis; Bozionelou, V.; Agelaki, Sofia; Perraki, Maria; Apostolaki, Stella; Kallergi, Galatea; Kalbakis, K.; Xyrafas, A.; Mavroudis, Dimitris

doi:10.1093/annonc/mds020

Cited by 143 publications

(101 citation statements)

References 35 publications

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“…Clinical implication of CTCs regarding the patients' prognosis as well as different therapeutic options based on their particular phenotypic and molecular characteristics have already been reported [2,8,11,31]. Therefore, the effective isolation of CTCs is a really critical step for further understanding of their biological and clinical relevance; however, there is no standard methodology for this.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs)

Kallergi

Politaki²,

Alkahtani³

et al. 2016

Cell Physiol Biochem

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Background: Detection of CTCs is a poor prognostic factor for many cancer types; however, their very low frequency represents an obstacle for their detection. The objective of the current study was to compare the performance of commonly used methods for CTCs isolation. Methods: The evaluated methods using spiking experiments of MCF7, SKBR3 and MDA MB-231 breast cancer cell lines were (i) ficoll density gradient separation (DGS), (ii) red blood cell lysis (Erythrolysis) isolation, (iii) positive immunomagnetic selection (EpCAM Dynal beads), (iv) two different negative immunomagnetic separation systems (Dynal vs Miltenyi CD45 beads) as well as (v) the Cell Search platform and (vi) the ISET system. Results: The recovery rates of Erythrolysis and DGS were 39% and 24%, respectively. Magnetic isolations are ranked from the worse to the best recovery rate as follows:, Myltenyi-anti-CD45 microbeads (24%); Dynal-anti-EpCAM beads (75%); Dynabeads-anti-CD45 (97%). CTCs isolation from blood samples using the CellSearch and ISET systems revealed that the recovery rate for Cell Search and ISET was 52% and 95%, respectively. Conclusions: Dynal-anti-CD45 beads have the best recovery rate compared to other magnetic methods. Furthermore the recovery rate of ISET was higher compared to Cell Search, especially for the more aggressive MDA-MB 231 cell line.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs)

Kallergi

Politaki²,

Alkahtani³

et al. 2016

Cell Physiol Biochem

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“…For this population, there is a need for more effective treatment than standard chemotherapy ( 104 ). The randomized phase II study by Georgoulias and colleagues indicated that trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapyresistant CTCs ( 105 ).…”

Section: Chemotherapy Switch Based On Ctc Enumerationmentioning

confidence: 99%

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

2016

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ABSTRACT"Liquid biopsy" focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratifi cation of patients based on the detection of therapeutic targets or resistance mechanisms. Signifi cance:The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specifi city and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratifi cation based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479-91.

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“…Such analyses may also include downstream components within signaltransducing pathways that influence new targeted therapies [e.g., KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in EGFR-targeted therapies, or PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; formerly known as PI3K) mutations in HER2-targeted therapies]. Moreover, administration of trastuzumab could eliminate chemotherapy-resistant CK19 mRNApositive CTCs, reduce the risk of disease recurrence, and prolong the disease-free survival time (42 ).…”

Section: Ctc Analysis As a Real-time Liquid Biopsymentioning

confidence: 99%

Circulating Tumor Cells: Liquid Biopsy of Cancer

2013

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BACKGROUND:The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with Ͼ400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients.CONTENT: This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecularcharacterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelialmesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells).

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Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study

Abstract: Administration of trastuzumab can eliminate chemotherapy-resistant CK19 mRNA-positive CTCs, reduce the risk of disease recurrence and prolong the DFS.

Cited by 143 publications

References 35 publications

Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs)

Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs)

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy

Circulating Tumor Cells: Liquid Biopsy of Cancer

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