Open AccessDetection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform
Author(s) -
YoonSim Yap,
Man Chun Leong,
Yong Wei Chua,
Kiley Wei-Jen Loh,
Guek Eng Lee,
Elaine Lim,
Rebecca Dent,
Raymond Ng,
John Lim,
Garima Singh,
Angela Tan,
Guofeng Guan,
Andrew Wu,
Yi Fang Lee,
Ali Asgar S. Bhagat,
Darren Wan-Teck Lim
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221305
Subject(s) - circulating tumor cell , medicine , hazard ratio , metastatic breast cancer , oncology , breast cancer , progression free survival , proportional hazards model , cancer , gastroenterology , overall survival , metastasis , confidence interval
Objectives 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. Results 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. Conclusions This work demonstrates the prognostic significance of CTCs in mBC detected using a label-free size-based enrichment platform.