Expression of activated type I receptor tyrosine kinases in early breast cancer
Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in pat...
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| Veröffentlicht in: | Breast cancer research and treatment 2012-07, Vol.134 (2), p.701-708 |
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| creator | Spears, Melanie Pederson, Hans Christian Lyttle, Nicola Gray, Claire Quintayo, Mary Anne Brogan, Lyndsay J Thomas, Jeremy St Kerr, Gillian R. Jack, Wilma J. L. Kunkler, Ian H. Cameron, David A. Chetty, Udi Bartlett, John M. S. |
| description | Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22–2.26,
p
= 0.001 and HR: 1.57, 95 % CI 1.22–2.03,
p
= 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23–2.18,
p
= 0.001 and HR: 1.55, 95 % CI 1.23–1.97,
p
= 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50–0.91,
p
= 0.01) and DRFS (HR: 0.73, 95 % CI 0.56–0.96,
p
= 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup. |
| doi_str_mv | 10.1007/s10549-012-2076-7 |
| format | Article |
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p
= 0.001 and HR: 1.57, 95 % CI 1.22–2.03,
p
= 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23–2.18,
p
= 0.001 and HR: 1.55, 95 % CI 1.23–1.97,
p
= 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50–0.91,
p
= 0.01) and DRFS (HR: 0.73, 95 % CI 0.56–0.96,
p
= 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-012-2076-7</identifier><identifier>PMID: 22562124</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Analysis ; Antineoplastic Agents, Hormonal - therapeutic use ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - mortality ; Cancer research ; Cancer therapies ; Care and treatment ; Clinical Trial ; Cohort Studies ; Disease-Free Survival ; Enzyme Activation ; Epidermal growth factor ; Female ; Gynecology. Andrology. Obstetrics ; Humans ; Kaplan-Meier Estimate ; Mammary gland diseases ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Phenols ; Phosphorylation ; Phosphotransferases ; Protein Processing, Post-Translational ; Proteins ; Receptor, Epidermal Growth Factor - metabolism ; Receptor, ErbB-2 - metabolism ; Receptor, ErbB-3 - metabolism ; Receptors, Estrogen - metabolism ; Tamoxifen - therapeutic use ; Tissue Array Analysis ; Tumors ; Tyrosine</subject><ispartof>Breast cancer research and treatment, 2012-07, Vol.134 (2), p.701-708</ispartof><rights>Springer Science+Business Media, LLC. 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Springer</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-523ea1ec78c5bf8a89a5a3f18a6e387754a767874011d69d595a540cba3efd503</citedby><cites>FETCH-LOGICAL-c500t-523ea1ec78c5bf8a89a5a3f18a6e387754a767874011d69d595a540cba3efd503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-012-2076-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-012-2076-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26200830$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22562124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spears, Melanie</creatorcontrib><creatorcontrib>Pederson, Hans Christian</creatorcontrib><creatorcontrib>Lyttle, Nicola</creatorcontrib><creatorcontrib>Gray, Claire</creatorcontrib><creatorcontrib>Quintayo, Mary Anne</creatorcontrib><creatorcontrib>Brogan, Lyndsay</creatorcontrib><creatorcontrib>J Thomas, Jeremy St</creatorcontrib><creatorcontrib>Kerr, Gillian R.</creatorcontrib><creatorcontrib>Jack, Wilma J. L.</creatorcontrib><creatorcontrib>Kunkler, Ian H.</creatorcontrib><creatorcontrib>Cameron, David A.</creatorcontrib><creatorcontrib>Chetty, Udi</creatorcontrib><creatorcontrib>Bartlett, John M. S.</creatorcontrib><title>Expression of activated type I receptor tyrosine kinases in early breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22–2.26,
p
= 0.001 and HR: 1.57, 95 % CI 1.22–2.03,
p
= 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23–2.18,
p
= 0.001 and HR: 1.55, 95 % CI 1.23–1.97,
p
= 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50–0.91,
p
= 0.01) and DRFS (HR: 0.73, 95 % CI 0.56–0.96,
p
= 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.</description><subject>Analysis</subject><subject>Antineoplastic Agents, Hormonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - mortality</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Clinical Trial</subject><subject>Cohort Studies</subject><subject>Disease-Free Survival</subject><subject>Enzyme Activation</subject><subject>Epidermal growth factor</subject><subject>Female</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Mammary gland diseases</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Phenols</subject><subject>Phosphorylation</subject><subject>Phosphotransferases</subject><subject>Protein Processing, Post-Translational</subject><subject>Proteins</subject><subject>Receptor, Epidermal Growth Factor - metabolism</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Receptor, ErbB-3 - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Tamoxifen - therapeutic use</subject><subject>Tissue Array Analysis</subject><subject>Tumors</subject><subject>Tyrosine</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kV1rFDEUhoModq3-AG8kIIo3U5PM5GMuS6laKPRGr8PZzJk2dTZZk0xx_70ZdrWtKLkIOXnO1_sS8pqzE86Y_pg5k13fMC4awbRq9BOy4lK3jRZcPyUrxpVulGHqiLzI-ZYx1mvWPydHQkgluOhW5Or85zZhzj4GGkcKrvg7KDjQstsivaAJHW5LTPWdYvYB6XcfIGOmPlCENO3oOiHkQh0Eh-kleTbClPHV4T4m3z6dfz370lxefb44O71snGSsNFK0CBydNk6uRwOmBwntyA0obI3WsgOttNEd43xQ_SB7CbJjbg0tjoNk7TH5sK-7TfHHjLnYjc8OpwkCxjlbzoRWpq6pK_r2L_Q2zinU6SrV1gZGKHFPXcOE1ocxlgRuKWpPW6m6rmraVerkH1Q9A268iwFHX-OPEt4_SLhBmMpNjtNcquD5Mcj3oKs654Sj3Sa_gbSrQ9rFbbt321a37eK2XTZ7c9hsXm9w-JPx294KvDsAkB1MY6oe-XzPKcGYaRc1xZ7L9StcY3oo0f-6_wLI_r3X</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>Spears, Melanie</creator><creator>Pederson, Hans Christian</creator><creator>Lyttle, Nicola</creator><creator>Gray, Claire</creator><creator>Quintayo, Mary Anne</creator><creator>Brogan, Lyndsay</creator><creator>J Thomas, Jeremy St</creator><creator>Kerr, Gillian R.</creator><creator>Jack, Wilma J. 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Obstetrics</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Mammary gland diseases</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Phenols</topic><topic>Phosphorylation</topic><topic>Phosphotransferases</topic><topic>Protein Processing, Post-Translational</topic><topic>Proteins</topic><topic>Receptor, Epidermal Growth Factor - metabolism</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Receptor, ErbB-3 - metabolism</topic><topic>Receptors, Estrogen - metabolism</topic><topic>Tamoxifen - therapeutic use</topic><topic>Tissue Array Analysis</topic><topic>Tumors</topic><topic>Tyrosine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spears, Melanie</creatorcontrib><creatorcontrib>Pederson, Hans Christian</creatorcontrib><creatorcontrib>Lyttle, Nicola</creatorcontrib><creatorcontrib>Gray, Claire</creatorcontrib><creatorcontrib>Quintayo, Mary Anne</creatorcontrib><creatorcontrib>Brogan, Lyndsay</creatorcontrib><creatorcontrib>J Thomas, Jeremy St</creatorcontrib><creatorcontrib>Kerr, Gillian R.</creatorcontrib><creatorcontrib>Jack, Wilma J. L.</creatorcontrib><creatorcontrib>Kunkler, Ian H.</creatorcontrib><creatorcontrib>Cameron, David A.</creatorcontrib><creatorcontrib>Chetty, Udi</creatorcontrib><creatorcontrib>Bartlett, John M. 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L.</au><au>Kunkler, Ian H.</au><au>Cameron, David A.</au><au>Chetty, Udi</au><au>Bartlett, John M. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of activated type I receptor tyrosine kinases in early breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>134</volume><issue>2</issue><spage>701</spage><epage>708</epage><pages>701-708</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22–2.26,
p
= 0.001 and HR: 1.57, 95 % CI 1.22–2.03,
p
= 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23–2.18,
p
= 0.001 and HR: 1.55, 95 % CI 1.23–1.97,
p
= 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50–0.91,
p
= 0.01) and DRFS (HR: 0.73, 95 % CI 0.56–0.96,
p
= 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22562124</pmid><doi>10.1007/s10549-012-2076-7</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2012-07, Vol.134 (2), p.701-708 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1027682567 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Analysis Antineoplastic Agents, Hormonal - therapeutic use Biological and medical sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - mortality Cancer research Cancer therapies Care and treatment Clinical Trial Cohort Studies Disease-Free Survival Enzyme Activation Epidermal growth factor Female Gynecology. Andrology. Obstetrics Humans Kaplan-Meier Estimate Mammary gland diseases Medical prognosis Medical sciences Medicine Medicine & Public Health Middle Aged Oncology Phenols Phosphorylation Phosphotransferases Protein Processing, Post-Translational Proteins Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - metabolism Receptor, ErbB-3 - metabolism Receptors, Estrogen - metabolism Tamoxifen - therapeutic use Tissue Array Analysis Tumors Tyrosine |
| title | Expression of activated type I receptor tyrosine kinases in early breast cancer |
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