Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform

Autoři: Yoon-Sim Yap aff001;  Man Chun Leong aff002;  Yong Wei Chua aff003;  Kiley Wei Jen Loh aff001;  Guek Eng Lee aff001;  Elaine Hsuen Lim aff001;  Rebecca Dent aff001;  Raymond Chee Hui Ng aff001;  John Heng-Chi Lim aff005;  Garima Singh aff002;  Angela Tan aff002;  Guofeng Guan aff002;  Andrew Wu aff002;  Yi Fang Lee aff002;  Ali Asgar S. Bhagat aff002;  Darren Wan-Teck Lim aff001
Působiště autorů: Division of Medical Oncology, National Cancer Centre Singapore, Singapore aff001;  Biolidics Ltd, Singapore aff002;  Department of Pathology, Singapore General Hospital, Singapore aff003;  Institute of Molecular and Cell Biology, A*Star, Singapore aff004;  Clinical Trials and Epidemiology Office, National Cancer Centre Singapore, Singapore aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221305



We aimed to study the prevalence of CTCs in breast cancer (BC) patients undergoing neoadjuvant or palliative therapy with a label-free microfluidic platform (ClearCell FX), and its prognostic relevance in metastatic BC (mBC).

Materials and methods

Peripheral blood samples were collected from 108 BC patients before starting a new line of treatment (“baseline”), majority of whom had mBC (76/108; 70.4%). CTCs were retrieved by dean flow fractionation that enriched for larger cells, and enumerated using immunofluorescence-based staining. Progression-free survival (PFS) in mBC patients was analysed using Kaplan-Meier method; cox proportional hazard models were used for univariable and multivariable analyses.


The detection rate of CTCs before starting a new line of treatment was 75.9% (n = 108; median: 8 CTCs/7.5 ml blood) at a cut off of ≥2 CTCs. PFS was inferior for mBC patients with baseline CTC count ≥5 CTCs/7.5 ml blood vs. those with < 5 CTCs/7.5 ml blood (median PFS: 4.3 vs. 7.0 months; p-value: 0.037). The prognostic relevance of CTCs was most significant in patients with HER2- mBC (median PFS: 4.1 vs. 8.3 months; p-value: 0.032), luminal (HR+HER2-) subtype (median PFS: 4.2 vs. 8.3 months; p-value: 0.048), and patients who had one or more prior treatments (median PFS: 4.2 vs. 7.0 months; p-value: 0.02). On multivariable analysis, baseline CTC level (hazard ratio (HR): 1.84, p-value: 0.02) and pre-treatment status (HR: 1.87, p-value: 0.05) were independent predictors of PFS.


This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.

Klíčová slova:

Blood – Blood counts – Breast cancer – Cancer treatment – Hormones – Metastasis – Prognosis – Microfluidics


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