CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy
Purpose Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endo...
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| Veröffentlicht in: | Breast cancer research and treatment 2019-12, Vol.178 (3), p.535-544 |
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| creator | Alfarsi, Lutfi H. Ansari, Rokaya El Craze, Madeleine L. Toss, Michael S. Masisi, Brendah Ellis, Ian O. Rakha, Emad A. Green, Andrew R. |
| description | Purpose
Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.
Methods
The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.
Results
High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (
P
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| doi_str_mv | 10.1007/s10549-019-05420-8 |
| format | Article |
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Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.
Methods
The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.
Results
High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (
P
< 0.0001) in patients with ER+ breast cancer. High CDC20 mRNA expression was significantly associated with poor patient outcome (
P
< 0.0001). Importantly, high CDC20 expression was correlated with poor response to endocrine treatment in patients who treated with hormonal therapy only (
P
< 0.01). In multivariate analysis, CDC20 mRNA was an independent predictor of poor clinical outcome after treatment with endocrine therapy (
P
= 0.02).
Conclusion
CDC20 is a candidate biomarker for a subgroup of ER+ breast cancer characterised by poor clinical outcome. This study shows that the CDC20 could act as potential predictive biomarker of poor response to endocrine therapy in ER+ breast cancer.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-019-05420-8</identifier><identifier>PMID: 31471836</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Antineoplastic Agents, Hormonal - therapeutic use ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Breast Neoplasms - therapy ; Cancer research ; Cdc20 Proteins - genetics ; Cdc20 Proteins - metabolism ; Cell division ; Cell Proliferation - genetics ; Clinical outcomes ; Cohort Studies ; Cytoplasm - metabolism ; Development and progression ; Drug Resistance, Neoplasm ; Endocrine therapy ; Estrogen ; Female ; Gene expression ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Medical colleges ; Medicine ; Medicine & Public Health ; Menopause ; Multivariate analysis ; Oncology ; Patients ; Preclinical Study ; Prognosis ; Receptors, Estrogen - metabolism ; RNA ; RNA, Messenger - genetics ; Solid tumors ; Survival Analysis ; Tumorigenesis</subject><ispartof>Breast cancer research and treatment, 2019-12, Vol.178 (3), p.535-544</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Breast Cancer Research and Treatment is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c473t-771c12537d8b10e6bbc85b532caffdc0db89975906e06eb45b99a9c4e1761bdc3</citedby><cites>FETCH-LOGICAL-c473t-771c12537d8b10e6bbc85b532caffdc0db89975906e06eb45b99a9c4e1761bdc3</cites><orcidid>0000-0002-0488-5913</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-019-05420-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-019-05420-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31471836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alfarsi, Lutfi H.</creatorcontrib><creatorcontrib>Ansari, Rokaya El</creatorcontrib><creatorcontrib>Craze, Madeleine L.</creatorcontrib><creatorcontrib>Toss, Michael S.</creatorcontrib><creatorcontrib>Masisi, Brendah</creatorcontrib><creatorcontrib>Ellis, Ian O.</creatorcontrib><creatorcontrib>Rakha, Emad A.</creatorcontrib><creatorcontrib>Green, Andrew R.</creatorcontrib><title>CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.
Methods
The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.
Results
High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (
P
< 0.0001) in patients with ER+ breast cancer. High CDC20 mRNA expression was significantly associated with poor patient outcome (
P
< 0.0001). Importantly, high CDC20 expression was correlated with poor response to endocrine treatment in patients who treated with hormonal therapy only (
P
< 0.01). In multivariate analysis, CDC20 mRNA was an independent predictor of poor clinical outcome after treatment with endocrine therapy (
P
= 0.02).
Conclusion
CDC20 is a candidate biomarker for a subgroup of ER+ breast cancer characterised by poor clinical outcome. This study shows that the CDC20 could act as potential predictive biomarker of poor response to endocrine therapy in ER+ breast cancer.</description><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Breast Neoplasms - therapy</subject><subject>Cancer research</subject><subject>Cdc20 Proteins - genetics</subject><subject>Cdc20 Proteins - metabolism</subject><subject>Cell division</subject><subject>Cell Proliferation - genetics</subject><subject>Clinical outcomes</subject><subject>Cohort Studies</subject><subject>Cytoplasm - metabolism</subject><subject>Development and progression</subject><subject>Drug Resistance, Neoplasm</subject><subject>Endocrine therapy</subject><subject>Estrogen</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Menopause</subject><subject>Multivariate analysis</subject><subject>Oncology</subject><subject>Patients</subject><subject>Preclinical Study</subject><subject>Prognosis</subject><subject>Receptors, Estrogen - metabolism</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>Solid tumors</subject><subject>Survival Analysis</subject><subject>Tumorigenesis</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kk2PFCEQhonRuOPqH_BgSEyMl16haZrmuBk_k0286JkAXT3D2gMtMBv35F-3xlld1xgDhFD1vAUVXkKecnbGGVOvCmey0w3juGTXsma4R1ZcKtGolqv7ZMV4r5p-YP0JeVTKJWNMK6YfkhPBO8UH0a_I9_XrdcsofFsylBJSpCHSBKXmtIFIM3hYasp0SSXUcAXUZbClUm-jBwxnGIOvBfMHCEURwUJtHOls_ReaJqxRlhQL0JooxDH5HCIetpDtcv2YPJjsXODJzX5KPr9982n9vrn4-O7D-vyi8Z0StVGKe95KocbBcQa9c36QTorW22kaPRvdoLWSmvWA03XSaW2174CrnrvRi1Py8lgX3_h1j_2ZXSge5tlGSPti2nYQnGm8AtHnf6GXaZ8jvu5AtUoMWna31MbOYEKcUs3WH4qa854pPfRCSqTO_kHhGGEXfIowBYzfEbz4Q7AFO9dtSfO-4teUu2B7BH1OpWSYzJLDzuZrw5k52MMc7WHQHuanPcyAomc3re3dDsbfkl9-QEAcgYKpuIF82_t_yv4Ao13Eug</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Alfarsi, Lutfi H.</creator><creator>Ansari, Rokaya El</creator><creator>Craze, Madeleine L.</creator><creator>Toss, Michael S.</creator><creator>Masisi, Brendah</creator><creator>Ellis, Ian O.</creator><creator>Rakha, Emad A.</creator><creator>Green, Andrew R.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0488-5913</orcidid></search><sort><creationdate>20191201</creationdate><title>CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy</title><author>Alfarsi, Lutfi H. ; Ansari, Rokaya El ; Craze, Madeleine L. ; Toss, Michael S. ; Masisi, Brendah ; Ellis, Ian O. ; Rakha, Emad A. ; Green, Andrew R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c473t-771c12537d8b10e6bbc85b532caffdc0db89975906e06eb45b99a9c4e1761bdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antineoplastic Agents, Hormonal - therapeutic use</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Breast Neoplasms - therapy</topic><topic>Cancer research</topic><topic>Cdc20 Proteins - genetics</topic><topic>Cdc20 Proteins - metabolism</topic><topic>Cell division</topic><topic>Cell Proliferation - genetics</topic><topic>Clinical outcomes</topic><topic>Cohort Studies</topic><topic>Cytoplasm - metabolism</topic><topic>Development and progression</topic><topic>Drug Resistance, Neoplasm</topic><topic>Endocrine therapy</topic><topic>Estrogen</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Menopause</topic><topic>Multivariate analysis</topic><topic>Oncology</topic><topic>Patients</topic><topic>Preclinical Study</topic><topic>Prognosis</topic><topic>Receptors, Estrogen - metabolism</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>Solid tumors</topic><topic>Survival Analysis</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alfarsi, Lutfi H.</creatorcontrib><creatorcontrib>Ansari, Rokaya El</creatorcontrib><creatorcontrib>Craze, Madeleine L.</creatorcontrib><creatorcontrib>Toss, Michael S.</creatorcontrib><creatorcontrib>Masisi, Brendah</creatorcontrib><creatorcontrib>Ellis, Ian O.</creatorcontrib><creatorcontrib>Rakha, Emad A.</creatorcontrib><creatorcontrib>Green, Andrew R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alfarsi, Lutfi H.</au><au>Ansari, Rokaya El</au><au>Craze, Madeleine L.</au><au>Toss, Michael S.</au><au>Masisi, Brendah</au><au>Ellis, Ian O.</au><au>Rakha, Emad A.</au><au>Green, Andrew R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>178</volume><issue>3</issue><spage>535</spage><epage>544</epage><pages>535-544</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><abstract>Purpose
Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.
Methods
The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.
Results
High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (
P
< 0.0001) in patients with ER+ breast cancer. High CDC20 mRNA expression was significantly associated with poor patient outcome (
P
< 0.0001). Importantly, high CDC20 expression was correlated with poor response to endocrine treatment in patients who treated with hormonal therapy only (
P
< 0.01). In multivariate analysis, CDC20 mRNA was an independent predictor of poor clinical outcome after treatment with endocrine therapy (
P
= 0.02).
Conclusion
CDC20 is a candidate biomarker for a subgroup of ER+ breast cancer characterised by poor clinical outcome. This study shows that the CDC20 could act as potential predictive biomarker of poor response to endocrine therapy in ER+ breast cancer.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31471836</pmid><doi>10.1007/s10549-019-05420-8</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0488-5913</orcidid></addata></record> |
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| ispartof | Breast cancer research and treatment, 2019-12, Vol.178 (3), p.535-544 |
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| language | eng |
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| subjects | Antineoplastic Agents, Hormonal - therapeutic use Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - therapy Cancer research Cdc20 Proteins - genetics Cdc20 Proteins - metabolism Cell division Cell Proliferation - genetics Clinical outcomes Cohort Studies Cytoplasm - metabolism Development and progression Drug Resistance, Neoplasm Endocrine therapy Estrogen Female Gene expression Gene Expression Regulation, Neoplastic Humans Immunohistochemistry Medical colleges Medicine Medicine & Public Health Menopause Multivariate analysis Oncology Patients Preclinical Study Prognosis Receptors, Estrogen - metabolism RNA RNA, Messenger - genetics Solid tumors Survival Analysis Tumorigenesis |
| title | CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy |
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