Yun June, Angela Tan

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gmstyja@nus.edu.sg


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DUKE-NUS MEDICAL SCHOOL
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    Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform
    (PUBLIC LIBRARY SCIENCE, 2019-09-25) Yap, Yoon-Sim; Leong, Man Chun; Chua, Yong Wei; Loh, Kiley Wei Jen; Lee, Guek Eng; Lim, Elaine Hsuen; Dent, Rebecca; Ng, Raymond Chee Hui; Lim, John Heng-Chi; Singh, Garima; Tan, Angela; Guan, Guofeng; Wu, Andrew; Lee, Yi Fang; Bhagat, Ali Asgar S; Lim, Darren Wan-Teck; Assoc Prof Wan-Teck Darren Lim; MEDICINE; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL); DUKE-NUS MEDICAL SCHOOL
    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.