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Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer
The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the ESR1 gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients...
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| Published in: | Breast cancer research and treatment 2011-06, Vol.127 (2), p.345-355 |
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| container_title | Breast cancer research and treatment |
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| creator | Nielsen, Kirsten Vang Ejlertsen, Bent Müller, Sven Møller, Susanne Rasmussen, Birgitte B. Balslev, Eva Lænkholm, Anne-Vibeke Christiansen, Peer Mouridsen, Henning T. |
| description | The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the
ESR1
gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients allocated to 5 years tamoxifen, we identified 61 patients with recurrence less than 4 years and 48 patients without recurrence at least 7 years after initiation of adjuvant tamoxifen. Archival tissue containing primary tumor was collected from 97 patients (89%). Tumor samples were analyzed for
ESR1
copy number changes using FISH with a probe covering the
ESR1
gene at 6q25 and a reference probe covering the centromere of chromosome 6. The assay was validated in a material of 120 normal breast samples. FISH analysis for
ESR1
was successful in 91 patients (94%). Amplification (ratio
ESR1
/CEN-6 ≥ 2.0) was observed in 11 of 50 (22%) patients with early recurrence, compared to two of 41 (5%) patients without recurrence. The difference is statistically significant (
P
= 0.033). In both groups, two patients with
ESR1
deletion (ratio
ESR1
/CEN-6 |
| doi_str_mv | 10.1007/s10549-010-0984-y |
| format | article |
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ESR1
gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients allocated to 5 years tamoxifen, we identified 61 patients with recurrence less than 4 years and 48 patients without recurrence at least 7 years after initiation of adjuvant tamoxifen. Archival tissue containing primary tumor was collected from 97 patients (89%). Tumor samples were analyzed for
ESR1
copy number changes using FISH with a probe covering the
ESR1
gene at 6q25 and a reference probe covering the centromere of chromosome 6. The assay was validated in a material of 120 normal breast samples. FISH analysis for
ESR1
was successful in 91 patients (94%). Amplification (ratio
ESR1
/CEN-6 ≥ 2.0) was observed in 11 of 50 (22%) patients with early recurrence, compared to two of 41 (5%) patients without recurrence. The difference is statistically significant (
P
= 0.033). In both groups, two patients with
ESR1
deletion (ratio
ESR1
/CEN-6 < 0.8) were identified.
ESR1
amplification was significantly associated with poor disease-free survival (
P
= 0.0054) and overall survival (
P
= 0.0004). This pilot study supports our hypothesis that
ESR1
amplification is associated with a poorer outcome following adjuvant treatment with tamoxifen in ER positive early breast cancer. This study also revealed the existence of
ESR1
deletions. The prognostic and predictive impact of
ESR1
copy number changes needs further exploration in clinical trials.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-010-0984-y</identifier><identifier>PMID: 20556506</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Aged ; Analysis ; Antineoplastic Agents, Hormonal - therapeutic use ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Cancer research ; Cancer therapies ; Chemotherapy, Adjuvant ; Drug resistance ; Drug Resistance, Neoplasm - genetics ; Endocrine therapy ; Estrogen ; Estrogen Receptor alpha - genetics ; Female ; Gene amplification ; Gene Amplification - genetics ; Gene Deletion ; Gene Order ; Gynecology. Andrology. Obstetrics ; Hormones ; Humans ; Mammary gland diseases ; Medical research ; Medical sciences ; Medicine ; Medicine & Public Health ; Medicine, Experimental ; Middle Aged ; Oncology ; Pilot Projects ; Postmenopausal women ; Postmenopause ; Preclinical Study ; Prognosis ; Survival Analysis ; Tamoxifen ; Tamoxifen - therapeutic use ; Tumors</subject><ispartof>Breast cancer research and treatment, 2011-06, Vol.127 (2), p.345-355</ispartof><rights>Springer Science+Business Media, LLC. 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Springer</rights><rights>Springer Science+Business Media, LLC. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-e326b26b0c98c11c45ef24acd6b708c05346e9503e71f0431ec1df3f8197e3633</citedby><cites>FETCH-LOGICAL-c541t-e326b26b0c98c11c45ef24acd6b708c05346e9503e71f0431ec1df3f8197e3633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24166749$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20556506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nielsen, Kirsten Vang</creatorcontrib><creatorcontrib>Ejlertsen, Bent</creatorcontrib><creatorcontrib>Müller, Sven</creatorcontrib><creatorcontrib>Møller, Susanne</creatorcontrib><creatorcontrib>Rasmussen, Birgitte B.</creatorcontrib><creatorcontrib>Balslev, Eva</creatorcontrib><creatorcontrib>Lænkholm, Anne-Vibeke</creatorcontrib><creatorcontrib>Christiansen, Peer</creatorcontrib><creatorcontrib>Mouridsen, Henning T.</creatorcontrib><title>Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the
ESR1
gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients allocated to 5 years tamoxifen, we identified 61 patients with recurrence less than 4 years and 48 patients without recurrence at least 7 years after initiation of adjuvant tamoxifen. Archival tissue containing primary tumor was collected from 97 patients (89%). Tumor samples were analyzed for
ESR1
copy number changes using FISH with a probe covering the
ESR1
gene at 6q25 and a reference probe covering the centromere of chromosome 6. The assay was validated in a material of 120 normal breast samples. FISH analysis for
ESR1
was successful in 91 patients (94%). Amplification (ratio
ESR1
/CEN-6 ≥ 2.0) was observed in 11 of 50 (22%) patients with early recurrence, compared to two of 41 (5%) patients without recurrence. The difference is statistically significant (
P
= 0.033). In both groups, two patients with
ESR1
deletion (ratio
ESR1
/CEN-6 < 0.8) were identified.
ESR1
amplification was significantly associated with poor disease-free survival (
P
= 0.0054) and overall survival (
P
= 0.0004). This pilot study supports our hypothesis that
ESR1
amplification is associated with a poorer outcome following adjuvant treatment with tamoxifen in ER positive early breast cancer. This study also revealed the existence of
ESR1
deletions. The prognostic and predictive impact of
ESR1
copy number changes needs further exploration in clinical trials.</description><subject>Aged</subject><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 - genetics</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Chemotherapy, Adjuvant</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Endocrine therapy</subject><subject>Estrogen</subject><subject>Estrogen Receptor alpha - genetics</subject><subject>Female</subject><subject>Gene amplification</subject><subject>Gene Amplification - genetics</subject><subject>Gene Deletion</subject><subject>Gene Order</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Hormones</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Experimental</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Pilot Projects</subject><subject>Postmenopausal women</subject><subject>Postmenopause</subject><subject>Preclinical Study</subject><subject>Prognosis</subject><subject>Survival Analysis</subject><subject>Tamoxifen</subject><subject>Tamoxifen - therapeutic use</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp1kV1rFDEUhgdRbK3-AG8kKHo39WQmHzOXS6kfUBD8uA7ZzEk3y0wyJpnW_Qv-arPsai1oEggkz_seznmr6jmFcwog3yYKnPU1UKih71i9e1CdUi7bWjZUPqxOgQpZiw7ESfUkpS0A9BL6x9VJA5wLDuK0-rma5tFZZ3R2wZNgyeWXz5RMekfmiIMzmURMLmXtDZIciB62y432mWQ9hR_OoifOkzmkPKEPs16SHslc3NDnRG5d3pBNiFPwWIwMzjnEPe2yu0GyjqhTJmZvHp9Wj6weEz473mfVt3eXXy8-1Fef3n-8WF3VhjOaa2wbsS4HTN8ZSg3jaBumzSDWEjoDvGUCew4tSmqBtRQNHWxrO9pLbEXbnlUvD75zDN8XTFltwxJ9Kak6wQSTIHmBXh2gaz2ict6GHLWZXDJq1XLRiLJYoc7_QZU94ORM6dm68n5P8OYvwQb1mDcpjMt--Ok-SA-giSGliFbN0U067hQFtQ9fHcJXJXy1D1_tiubFsbFlPeHwR_E77QK8PgI6GT3aWObu0h3HqBCS9YVrDlwqX_4a492E_l_9F94Yx5k</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Nielsen, Kirsten Vang</creator><creator>Ejlertsen, Bent</creator><creator>Müller, Sven</creator><creator>Møller, Susanne</creator><creator>Rasmussen, Birgitte B.</creator><creator>Balslev, Eva</creator><creator>Lænkholm, Anne-Vibeke</creator><creator>Christiansen, Peer</creator><creator>Mouridsen, Henning T.</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><scope>IQODW</scope><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>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>20110601</creationdate><title>Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer</title><author>Nielsen, Kirsten Vang ; Ejlertsen, Bent ; Müller, Sven ; Møller, Susanne ; Rasmussen, Birgitte B. ; Balslev, Eva ; Lænkholm, Anne-Vibeke ; Christiansen, Peer ; Mouridsen, Henning T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c541t-e326b26b0c98c11c45ef24acd6b708c05346e9503e71f0431ec1df3f8197e3633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Aged</topic><topic>Analysis</topic><topic>Antineoplastic Agents, Hormonal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Chemotherapy, Adjuvant</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Endocrine therapy</topic><topic>Estrogen</topic><topic>Estrogen Receptor alpha - genetics</topic><topic>Female</topic><topic>Gene amplification</topic><topic>Gene Amplification - genetics</topic><topic>Gene Deletion</topic><topic>Gene Order</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Hormones</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Experimental</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Pilot Projects</topic><topic>Postmenopausal women</topic><topic>Postmenopause</topic><topic>Preclinical Study</topic><topic>Prognosis</topic><topic>Survival Analysis</topic><topic>Tamoxifen</topic><topic>Tamoxifen - therapeutic use</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nielsen, Kirsten Vang</creatorcontrib><creatorcontrib>Ejlertsen, Bent</creatorcontrib><creatorcontrib>Müller, Sven</creatorcontrib><creatorcontrib>Møller, Susanne</creatorcontrib><creatorcontrib>Rasmussen, Birgitte B.</creatorcontrib><creatorcontrib>Balslev, Eva</creatorcontrib><creatorcontrib>Lænkholm, Anne-Vibeke</creatorcontrib><creatorcontrib>Christiansen, Peer</creatorcontrib><creatorcontrib>Mouridsen, Henning T.</creatorcontrib><collection>Pascal-Francis</collection><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>ProQuest Health and Medical</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)</collection><collection>ProQuest Central</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>ProQuest 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 China</collection><collection>ProQuest Central Basic</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nielsen, Kirsten Vang</au><au>Ejlertsen, Bent</au><au>Müller, Sven</au><au>Møller, Susanne</au><au>Rasmussen, Birgitte B.</au><au>Balslev, Eva</au><au>Lænkholm, Anne-Vibeke</au><au>Christiansen, Peer</au><au>Mouridsen, Henning T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>127</volume><issue>2</issue><spage>345</spage><epage>355</epage><pages>345-355</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>The estrogen receptor (ER) is the target of tamoxifen, but endocrine therapies do not benefit all patients with ER positive tumors. We therefore hypothesized that copy number changes in the
ESR1
gene, encoding ER, confer resistance. Within a consecutive series of ER positive, postmenopausal patients allocated to 5 years tamoxifen, we identified 61 patients with recurrence less than 4 years and 48 patients without recurrence at least 7 years after initiation of adjuvant tamoxifen. Archival tissue containing primary tumor was collected from 97 patients (89%). Tumor samples were analyzed for
ESR1
copy number changes using FISH with a probe covering the
ESR1
gene at 6q25 and a reference probe covering the centromere of chromosome 6. The assay was validated in a material of 120 normal breast samples. FISH analysis for
ESR1
was successful in 91 patients (94%). Amplification (ratio
ESR1
/CEN-6 ≥ 2.0) was observed in 11 of 50 (22%) patients with early recurrence, compared to two of 41 (5%) patients without recurrence. The difference is statistically significant (
P
= 0.033). In both groups, two patients with
ESR1
deletion (ratio
ESR1
/CEN-6 < 0.8) were identified.
ESR1
amplification was significantly associated with poor disease-free survival (
P
= 0.0054) and overall survival (
P
= 0.0004). This pilot study supports our hypothesis that
ESR1
amplification is associated with a poorer outcome following adjuvant treatment with tamoxifen in ER positive early breast cancer. This study also revealed the existence of
ESR1
deletions. The prognostic and predictive impact of
ESR1
copy number changes needs further exploration in clinical trials.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>20556506</pmid><doi>10.1007/s10549-010-0984-y</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2011-06, Vol.127 (2), p.345-355 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_proquest_journals_864647075 |
| source | Springer Nature |
| subjects | Aged Analysis Antineoplastic Agents, Hormonal - therapeutic use Biological and medical sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Cancer research Cancer therapies Chemotherapy, Adjuvant Drug resistance Drug Resistance, Neoplasm - genetics Endocrine therapy Estrogen Estrogen Receptor alpha - genetics Female Gene amplification Gene Amplification - genetics Gene Deletion Gene Order Gynecology. Andrology. Obstetrics Hormones Humans Mammary gland diseases Medical research Medical sciences Medicine Medicine & Public Health Medicine, Experimental Middle Aged Oncology Pilot Projects Postmenopausal women Postmenopause Preclinical Study Prognosis Survival Analysis Tamoxifen Tamoxifen - therapeutic use Tumors |
| title | Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer |
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