Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer

Abstract

In this novel time-dependent analysis of longitudinally collected CTCs and CTC-clusters, we showed that CTC-clusters added additional prognostic values to CTC enumeration alone, and a larger-size CTC-cluster conferred a higher risk of death in MBC patients.

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

“…A positive CTC count was associated with cancer risk, whereby a low CTC count (<0.3 CTC/ml) was correlated with mild malignant potential, 0.3-20 CTC/ml with moderate malignant potential, and a higher CTC count (>20 CTC/ml) with higher risk of malignancy, recurrence and metastasis, consistent with previous reports [1,2,4]. In addition to the CTC number, the type of cells, single cells or clusters, provide valuable insights into the cancer prognosis [3,4]. In this study we employed the ISET technology (Rarecells, France) [5] for CTC detection, which provides the advantage of a direct identification of malignant cells by cyto-morphological criteria [6], permitting distinction between precursor and malignant single cells and clusters, as well as reactive inflammatory atypical cells [9,16,17].…”

“…In a group of 177 women with metastatic breast cancer, CTC count was directly related to disease progression and survival, whereby a CTC count of less than 0.7 CTC/ml (5 CTC in 7.5 ml of whole blood) had a longer progression free survival and overall survival compared to a CTC count of more than 0.7 CTC/ml (median progression-free survival 2.7 months versus 7.0 months, p<0.001), and median overall survival (10.1 months versus >18 months, p<0.001) [1]. Furthermore, the type of CTC cells, either single cells or CTC clusters, are a prognostic predictor of metastasizing potential and overall survival, with a hazard ratio of 14.5 (p<0.001) for ≥ 3-cell CTC clusters compared to no CTC [3].Presence of CTC has also been associated with early carcinogenesis and risk of cancer [4]. In a study of cancer-free patients with chronic obstructive pulmonary disease (COPD), CTC were detected in 3% of the patients, who developed lung cancer within 1-4 years after CTC screening.…”

Liquid biopsy - emergence of a new era in personalized cancer care

“…Longitudinal analyses have, also, identified a link between the size of CTC-clusters and patient overall survival. Compared to the patients without any CTC, those with 2-cell CTC-clusters and ≥3-cell CTCclusters had a hazard ratio of 7.96 and 14.50 respectively [119,120]. Isolation of CTC with CellSearch CTC kit coupled with NGS on Roche 454 GS junior platform has proved successful in EGFR mutation analysis in the Phase II Erlotinib TRIGGER) study [121].…”

Epithelial–mesenchymal plasticity and circulating tumor cells: Travel companions to metastases

“…The possibility that these clusters might actually form during the processing of the blood samples during the CTC assay has been debated (Bednarz-Knoll et al, 2012), although they are much less prevalent than isolated CTCs. These clusters are today recognized as functional entities and have been detected in various types of cancers including breast, lung, pancreas, prostate, or kidney cancers (Molnar et al, 2001;Stott et al, 2010;Cho et al, 2012;Hou et al, 2012;Krebs et al, 2012;Yu et al, 2013;Aceto et al, 2014;Mu et al, 2015;Paoletti et al, 2015;Wang et al, 2017a).…”