Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer
The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamo...
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| creator | Alkner, Sara Bendahl, Pär-Ola Ehinger, Anna Lövgren, Kristina Rydén, Lisa Fernö, Mårten |
| description | The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.
From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.
CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.
Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance. |
| doi_str_mv | 10.1371/journal.pone.0150977 |
| format | Article |
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From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.
CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.
Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0150977</identifier><identifier>PMID: 26959415</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antineoplastic Agents, Hormonal - therapeutic use ; Biology and Life Sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Cancer ; Cancer and Oncology ; Cancer och onkologi ; Cancer therapies ; Chemotherapy ; Clinical Medicine ; Comparative analysis ; Complications and side effects ; Correlation ; Dosage and administration ; Drug therapy ; Endocrine therapy ; ErbB-2 protein ; Estrogen receptors ; Estrogens ; Female ; Gene expression ; Genetic aspects ; Humans ; In Vitro Techniques ; In vivo methods and tests ; Klinisk medicin ; Male ; Medical and Health Sciences ; Medical diagnosis ; Medical prognosis ; Medicin och hälsovetenskap ; Medicine and Health Sciences ; Metastasis ; Middle Aged ; Nuclear Receptor Coactivator 3 - metabolism ; Oncology ; Pathology ; Patients ; Physiological aspects ; Prognosis ; Radiation therapy ; Receptor, ErbB-2 - metabolism ; Receptors, Estrogen - metabolism ; Studies ; Tamoxifen ; Tamoxifen - therapeutic use ; Treatment resistance ; Tumors</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0150977-e0150977</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Alkner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Alkner et al 2016 Alkner et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c761t-4bea79346f80c0975cb9b9df0080c1012b304a5f8c26762e7ecf156cb197bd853</citedby><cites>FETCH-LOGICAL-c761t-4bea79346f80c0975cb9b9df0080c1012b304a5f8c26762e7ecf156cb197bd853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784945/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4784945/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,551,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26959415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/8852876$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Coleman, William B.</contributor><creatorcontrib>Alkner, Sara</creatorcontrib><creatorcontrib>Bendahl, Pär-Ola</creatorcontrib><creatorcontrib>Ehinger, Anna</creatorcontrib><creatorcontrib>Lövgren, Kristina</creatorcontrib><creatorcontrib>Rydén, Lisa</creatorcontrib><creatorcontrib>Fernö, Mårten</creatorcontrib><title>Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.
From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.
CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.
Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Lunds universitet</collection><collection>SwePub Articles full text</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>Alkner, Sara</au><au>Bendahl, Pär-Ola</au><au>Ehinger, Anna</au><au>Lövgren, Kristina</au><au>Rydén, Lisa</au><au>Fernö, Mårten</au><au>Coleman, William B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-03-09</date><risdate>2016</risdate><volume>11</volume><issue>3</issue><spage>e0150977</spage><epage>e0150977</epage><pages>e0150977-e0150977</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The estrogen receptor coactivator Amplified in Breast Cancer 1 (AIB1) has been associated with an improved response to adjuvant tamoxifen in breast cancer, but also with endocrine treatment resistance. We hereby use metachronous contralateral breast cancer (CBC) developed despite prior adjuvant tamoxifen for the first tumor as an "in vivo"-model for tamoxifen resistance. AIB1-expression in the presumable resistant (CBC after prior tamoxifen) and naïve setting (CBC without prior tamoxifen) is compared and correlated to prognosis after CBC.
From a well-defined population-based cohort of CBC-patients we have constructed a unique tissue-microarray including >700 patients.
CBC developed after adjuvant tamoxifen more often had a HER2-positive/triple negative-subtype and a high AIB1-expression (37% vs. 23%, p = 0.009), than if no prior endocrine treatment had been administered. In patients with an estrogen receptor (ER) positive CBC, a high AIB1-expression correlated to an inferior prognosis. However, these patients seemed to respond to tamoxifen, but only if endocrine therapy had not been administered for BC1.
Metachronous CBC developed after prior endocrine treatment has a decreased ER-expression and an increased HER2-expression. This is consistent with endocrine treatment escape mechanisms previously suggested, and indicates metachronous CBC to be a putative model for studies of treatment resistance "in vivo". The increased AIB1-expression in CBC developed after prior tamoxifen suggests a role of AIB1 in endocrine treatment resistance. In addition, we found indications that the response to tamoxifen in CBC with a high AIB1-expression seem to differ depending on previous exposure to this drug. A different function for AIB1 in the tamoxifen treatment naïve vs. resistant setting is suggested, and may explain previously conflicting results where a high AIB1-expression has been correlated to both a good response to adjuvant tamoxifen and tamoxifen resistance.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26959415</pmid><doi>10.1371/journal.pone.0150977</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-03, Vol.11 (3), p.e0150977-e0150977 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1771736464 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SWEPUB Freely available online; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Antineoplastic Agents, Hormonal - therapeutic use Biology and Life Sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Cancer Cancer and Oncology Cancer och onkologi Cancer therapies Chemotherapy Clinical Medicine Comparative analysis Complications and side effects Correlation Dosage and administration Drug therapy Endocrine therapy ErbB-2 protein Estrogen receptors Estrogens Female Gene expression Genetic aspects Humans In Vitro Techniques In vivo methods and tests Klinisk medicin Male Medical and Health Sciences Medical diagnosis Medical prognosis Medicin och hälsovetenskap Medicine and Health Sciences Metastasis Middle Aged Nuclear Receptor Coactivator 3 - metabolism Oncology Pathology Patients Physiological aspects Prognosis Radiation therapy Receptor, ErbB-2 - metabolism Receptors, Estrogen - metabolism Studies Tamoxifen Tamoxifen - therapeutic use Treatment resistance Tumors |
| title | Prior Adjuvant Tamoxifen Treatment in Breast Cancer Is Linked to Increased AIB1 and HER2 Expression in Metachronous Contralateral Breast Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-20T20%3A40%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Prior%20Adjuvant%20Tamoxifen%20Treatment%20in%20Breast%20Cancer%20Is%20Linked%20to%20Increased%20AIB1%20and%20HER2%20Expression%20in%20Metachronous%20Contralateral%20Breast%20Cancer&rft.jtitle=PloS%20one&rft.au=Alkner,%20Sara&rft.date=2016-03-09&rft.volume=11&rft.issue=3&rft.spage=e0150977&rft.epage=e0150977&rft.pages=e0150977-e0150977&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0150977&rft_dat=%3Cgale_plos_%3EA453531345%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1771736464&rft_id=info:pmid/26959415&rft_galeid=A453531345&rft_doaj_id=oai_doaj_org_article_a081fc09c1474223873cd8214a62e247&rfr_iscdi=true |