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

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). Peripheral blood samples were collected from 108 BC patients before starti...

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Veröffentlicht in:PloS one 2019-09, Vol.14 (9), p.e0221305-e0221305
Hauptverfasser: 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
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container_end_page e0221305
container_issue 9
container_start_page e0221305
container_title PloS one
container_volume 14
creator 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
description 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). 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.
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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 &lt; 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0221305</identifier><identifier>PMID: 31553731</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvant chemotherapy ; Adult ; Aged ; Asian Continental Ancestry Group ; Biology and Life Sciences ; Blood ; Breast cancer ; Breast Neoplasms - blood ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer metastasis ; Cancer research ; Cancer therapies ; Care and treatment ; Cell adhesion &amp; migration ; Cell Count ; Cell survival ; Chemotherapy ; EDTA ; Engineering and Technology ; ErbB-2 protein ; Female ; Fluorescent antibody technique ; Fractionation ; Humans ; Immunofluorescence ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lapatinib ; Medical prognosis ; Medical research ; Medicine and Health Sciences ; Metastases ; Metastasis ; Microfluidics ; Middle Aged ; Neoadjuvant therapy ; Neoplastic Cells, Circulating - pathology ; Oncology ; Pathology ; Peripheral blood ; Prognosis ; Progression-Free Survival ; Prospective Studies ; Receptor, ErbB-2 - metabolism ; Risk factors ; Sampling methods ; Singapore ; Statistical models ; Studies ; Tumors</subject><ispartof>PloS one, 2019-09, Vol.14 (9), p.e0221305-e0221305</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Yap et al. 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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.</description><subject>Adjuvant chemotherapy</subject><subject>Adult</subject><subject>Aged</subject><subject>Asian Continental Ancestry Group</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer metastasis</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell Count</subject><subject>Cell survival</subject><subject>Chemotherapy</subject><subject>EDTA</subject><subject>Engineering and Technology</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Fluorescent antibody technique</subject><subject>Fractionation</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Immunohistochemistry</subject><subject>Kaplan-Meier Estimate</subject><subject>Lapatinib</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Microfluidics</subject><subject>Middle Aged</subject><subject>Neoadjuvant therapy</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Peripheral blood</subject><subject>Prognosis</subject><subject>Progression-Free Survival</subject><subject>Prospective Studies</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Risk factors</subject><subject>Sampling methods</subject><subject>Singapore</subject><subject>Statistical models</subject><subject>Studies</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUstu1DAUjRCIloE_QGCJTVlk8COOk02l0fCqVIlNWVuOcz145NiDnVTiB_hunE5adVDlha3rc859naJ4S_CaMEE-7cMUvXLrQ_CwxpQShvmz4py0jJY1xez5o_dZ8SqlPcacNXX9sjhjhHMmGDkv_n6GEfRog0fK9-gQw86HNFqNIji4VV4DCgZpG_Xk1Gj9Do3TkFMjDc4ldLG92aaPyHq0SVZ51EVQaUR6JsaEpjQzFHKqA1eaCIAGq2MwbrJ9TnLImibE4XXxwiiX4M1yr4qfX7_cbL-X1z--XW0316XmLRtLUAbTVlWMGENx13KhCYOaNR03Ndas5l0FWANulQYOuO46hXHVsJYTgmnDVsX7o-7BhSSXESZJaSsIpYKzjLg6Ivqg9vIQ7aDiHxmUlXeBEHdSxTwfB5JkOKiOUuhFRYCpVlSG6qYVutI6i62KyyXb1A3Qa_BjVO5E9PTH219yF25lLWosxFzMxSIQw-8J0igHm-bBKw9huqu7IRWvGpqhH_6DPt3dgtqp3ID1JuS8ehaVmxpjUTFczVrrJ1D59JC3l_1mbI6fEKojIa82pQjmoUeC5ezW-2Lk7Fa5uDXT3j2ezwPp3p7sH7Ru5_E</recordid><startdate>20190925</startdate><enddate>20190925</enddate><creator>Yap, Yoon-Sim</creator><creator>Leong, Man Chun</creator><creator>Chua, Yong Wei</creator><creator>Loh, Kiley Wei Jen</creator><creator>Lee, Guek Eng</creator><creator>Lim, Elaine Hsuen</creator><creator>Dent, Rebecca</creator><creator>Ng, Raymond Chee Hui</creator><creator>Lim, John Heng-Chi</creator><creator>Singh, Garima</creator><creator>Tan, Angela</creator><creator>Guan, Guofeng</creator><creator>Wu, Andrew</creator><creator>Lee, Yi Fang</creator><creator>Bhagat, Ali Asgar S</creator><creator>Lim, Darren Wan-Teck</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4695-8762</orcidid><orcidid>https://orcid.org/0000-0002-0347-5066</orcidid></search><sort><creationdate>20190925</creationdate><title>Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-eaf029a431ff20b957c13e638b5f60c365b4e0ce09ace5e06bba0048395110283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adjuvant chemotherapy</topic><topic>Adult</topic><topic>Aged</topic><topic>Asian Continental Ancestry Group</topic><topic>Biology and Life Sciences</topic><topic>Blood</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yap, Yoon-Sim</au><au>Leong, Man Chun</au><au>Chua, Yong Wei</au><au>Loh, Kiley Wei Jen</au><au>Lee, Guek Eng</au><au>Lim, Elaine Hsuen</au><au>Dent, Rebecca</au><au>Ng, Raymond Chee Hui</au><au>Lim, John Heng-Chi</au><au>Singh, Garima</au><au>Tan, Angela</au><au>Guan, Guofeng</au><au>Wu, Andrew</au><au>Lee, Yi Fang</au><au>Bhagat, Ali Asgar S</au><au>Lim, Darren Wan-Teck</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-09-25</date><risdate>2019</risdate><volume>14</volume><issue>9</issue><spage>e0221305</spage><epage>e0221305</epage><pages>e0221305-e0221305</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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). 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 &lt; 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31553731</pmid><doi>10.1371/journal.pone.0221305</doi><orcidid>https://orcid.org/0000-0002-4695-8762</orcidid><orcidid>https://orcid.org/0000-0002-0347-5066</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adjuvant chemotherapy
Adult
Aged
Asian Continental Ancestry Group
Biology and Life Sciences
Blood
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cancer metastasis
Cancer research
Cancer therapies
Care and treatment
Cell adhesion & migration
Cell Count
Cell survival
Chemotherapy
EDTA
Engineering and Technology
ErbB-2 protein
Female
Fluorescent antibody technique
Fractionation
Humans
Immunofluorescence
Immunohistochemistry
Kaplan-Meier Estimate
Lapatinib
Medical prognosis
Medical research
Medicine and Health Sciences
Metastases
Metastasis
Microfluidics
Middle Aged
Neoadjuvant therapy
Neoplastic Cells, Circulating - pathology
Oncology
Pathology
Peripheral blood
Prognosis
Progression-Free Survival
Prospective Studies
Receptor, ErbB-2 - metabolism
Risk factors
Sampling methods
Singapore
Statistical models
Studies
Tumors
title Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform
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