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Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial.

Identifieur interne : 001F80 ( PubMed/Checkpoint ); précédent : 001F79; suivant : 001F81

Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial.

Auteurs : Sherene Loi [Australie] ; Urania Dafni [Grèce] ; Dimitris Karlis [Grèce] ; Varvara Polydoropoulou [Grèce] ; Brandon M. Young [États-Unis] ; Scooter Willis [États-Unis] ; Bradley Long [États-Unis] ; Evandro De Azambuja [Belgique] ; Christos Sotiriou [Belgique] ; Giuseppe Viale [Italie] ; Josef Rüschoff [Allemagne] ; Martine J. Piccart [Belgique] ; Mitch Dowsett [Royaume-Uni] ; Stefan Michiels [France] ; Brian Leyland-Jones [États-Unis]

Source :

RBID : pubmed:27100299

Descripteurs français

English descriptors

Abstract

A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown.

DOI: 10.1001/jamaoncol.2016.0339
PubMed: 27100299


Affiliations:


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pubmed:27100299

Le document en format XML

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<term>Estrogen Receptor alpha</term>
<term>Receptor, ErbB-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Estrogen Receptor alpha</term>
<term>RNA, Messenger</term>
<term>Receptor, ErbB-2</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Antineoplastic Agents</term>
<term>Trastuzumab</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Breast Neoplasms</term>
<term>Carcinoma</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Récepteur ErbB-2</term>
<term>Récepteur alpha des oestrogènes</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Breast Neoplasms</term>
<term>Carcinoma</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>ARN messager</term>
<term>Carcinomes</term>
<term>Récepteur ErbB-2</term>
<term>Récepteur alpha des oestrogènes</term>
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Carcinomes</term>
<term>Tumeurs du sein</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Antinéoplasiques</term>
<term>Trastuzumab</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Chemotherapy, Adjuvant</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Humans</term>
<term>Immunohistochemistry</term>
<term>In Situ Hybridization, Fluorescence</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Prognosis</term>
<term>Proportional Hazards Models</term>
<term>Randomized Controlled Trials as Topic</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Essais contrôlés randomisés comme sujet</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunohistochimie</term>
<term>Modèles de hasards proportionnels</term>
<term>Pronostic</term>
<term>Survie sans rechute</term>
<term>Technique FISH</term>
<term>Traitement médicamenteux adjuvant</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown.</div>
</front>
</TEI>
<pubmed>
<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">27100299</PMID>
<DateCreated>
<Year>2016</Year>
<Month>08</Month>
<Day>12</Day>
</DateCreated>
<DateCompleted>
<Year>2017</Year>
<Month>01</Month>
<Day>30</Day>
</DateCompleted>
<DateRevised>
<Year>2017</Year>
<Month>04</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print">
<Journal>
<ISSN IssnType="Electronic">2374-2445</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>2</Volume>
<Issue>8</Issue>
<PubDate>
<Year>2016</Year>
<Month>Aug</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>JAMA oncology</Title>
<ISOAbbreviation>JAMA Oncol</ISOAbbreviation>
</Journal>
<ArticleTitle>Effects of Estrogen Receptor and Human Epidermal Growth Factor Receptor-2 Levels on the Efficacy of Trastuzumab: A Secondary Analysis of the HERA Trial.</ArticleTitle>
<Pagination>
<MedlinePgn>1040-7</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1001/jamaoncol.2016.0339</ELocationID>
<Abstract>
<AbstractText Label="IMPORTANCE" NlmCategory="OBJECTIVE">A number of studies suggest that response to antihuman epidermal growth factor receptor-2 (currently known as ERBB2, butreferred to asHER2 in this study) agents differs by estrogen receptor (ER) level status. The clinical relevance of this is unknown.</AbstractText>
<AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To determine the magnitude of trastuzumab benefit according to quantitative levels of ER and HER2 in the HERceptin Adjuvant (HERA) trial.</AbstractText>
<AbstractText Label="DESIGN, SETTING, AND PARTICIPANTS" NlmCategory="METHODS">The HERA trial was an international, multicenter, randomized trial that included 5099 patients with early-stage HER2-positive breast cancer, randomized between 2001 and 2005 to receive either no trastuzumab or trastuzumab, after adjuvant chemotherapy. This is a secondary analysis of the HERA study. Local ER immunohistochemical (IHC) analyses, HER2 fluorescence in situ hybridization (FISH) ratio, and copy number results were available for 3037 patients (59.6%) randomized to observation and trastuzumab (1 or 2 years) (cohort 1). Transcript levels of ESR1 and HER2 genes were available for 615 patients (12.1%) (cohort 2).</AbstractText>
<AbstractText Label="INTERVENTIONS" NlmCategory="METHODS">Patients were randomized to receive either no trastuzumab or 1 year vs 2 years of trastuzumab. Endocrine therapy was given to patients with hormone receptor-positive disease as per local guidelines.</AbstractText>
<AbstractText Label="MAIN OUTCOMES AND MEASURES" NlmCategory="METHODS">Disease-free survival (DFS) and overall survival (OS) were the primary and secondary end points in the intent-to-treat population (ITT). Analyses adjusting for crossover (censored and inverse probability weighted [IPW]) were also performed. Interactions among treatment, ER status, and HER2 amplification using predefined cutoffs were assessed in Cox proportional hazards regression models.</AbstractText>
<AbstractText Label="RESULTS" NlmCategory="RESULTS">Median follow-up time was 8 years. Levels of FISH and HER2 copy numbers were significantly higher in ER-negative patients (P < .001). In cohort 1, for DFS and OS, a significant treatment effect was found for all ER, IHC, and FISH levels, except for the ER-positive/HER2 low FISH ratio (≥2 to <5) group (DFS: 3-way ITT Pvalue for interaction = .07; censored = .02; IPW = .03; OS ITT Pvalue for interaction = .007; censored = .04; IPW = .03). In cohort 2, consistent with cohort 1, a significant predictive effect of the ESR1 gene for both end points was also observed (DFS Pvalue for interaction = .06; OS = .02), indicating that breast cancers with higher ESR1 levels also derive less benefit from trastuzumab.</AbstractText>
<AbstractText Label="CONCLUSIONS AND RELEVANCE" NlmCategory="CONCLUSIONS">Patients with HER2-positive breast cancers that are ER-positive by IHC analyses with low FISH ratio (≥2 to <5), or with higher ESR1 levels derive significantly less benefit from adjuvant trastuzumab after chemotherapy. These data may explain heterogeneity in response to anti-HER2 agents in HER2-positive, ER-positive breast cancers as some may be more luminal-like than HER2 driven.</AbstractText>
<AbstractText Label="TRIAL REGISTRATION" NlmCategory="BACKGROUND">clinicaltrials.gov Identifier: NCT00045032.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Loi</LastName>
<ForeName>Sherene</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Division of Research and Clinical Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dafni</LastName>
<ForeName>Urania</ForeName>
<Initials>U</Initials>
<AffiliationInfo>
<Affiliation>Frontier Science Foundation- Hellas, Athens, Greece3University of Athens, Athens, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Karlis</LastName>
<ForeName>Dimitris</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>Frontier Science Foundation- Hellas, Athens, Greece4Athens University of Economics and Business, Athens, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Polydoropoulou</LastName>
<ForeName>Varvara</ForeName>
<Initials>V</Initials>
<AffiliationInfo>
<Affiliation>Frontier Science Foundation- Hellas, Athens, Greece.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Young</LastName>
<ForeName>Brandon M</ForeName>
<Initials>BM</Initials>
<AffiliationInfo>
<Affiliation>Avera Cancer Institute, Department of Molecular and Experimental Medicine, Sioux Falls, South Dakota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Willis</LastName>
<ForeName>Scooter</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Avera Cancer Institute, Department of Molecular and Experimental Medicine, Sioux Falls, South Dakota.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Long</LastName>
<ForeName>Bradley</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Department of Pathology, University of Chicago, Chicago, Illinois.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>de Azambuja</LastName>
<ForeName>Evandro</ForeName>
<Initials>E</Initials>
<AffiliationInfo>
<Affiliation>BREAST Datacentre, Institute Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Sotiriou</LastName>
<ForeName>Christos</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Breast Cancer Translational Research Laboratory, Institute Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Viale</LastName>
<ForeName>Giuseppe</ForeName>
<Initials>G</Initials>
<AffiliationInfo>
<Affiliation>University of Milan, European Institute of Oncology, Milan, Italy.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Rüschoff</LastName>
<ForeName>Josef</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Targos Molecular Pathology GmbH, Kassel, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Piccart</LastName>
<ForeName>Martine J</ForeName>
<Initials>MJ</Initials>
<AffiliationInfo>
<Affiliation>Department of Medicine, Institute Jules Bordet, Universite Libre de Bruxelles and Breast International Group (BIG), Brussels, Belgium12Breast International Group (BIG), Brussels, Belgium.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Dowsett</LastName>
<ForeName>Mitch</ForeName>
<Initials>M</Initials>
<AffiliationInfo>
<Affiliation>Royal Marsden Hospital, London, England.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Michiels</LastName>
<ForeName>Stefan</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>INSERM U1018 CESP, Service de Biostatistique et d'Epidémiologie, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Leyland-Jones</LastName>
<ForeName>Brian</ForeName>
<Initials>B</Initials>
<AffiliationInfo>
<Affiliation>Avera Cancer Institute, Department of Molecular and Experimental Medicine, Sioux Falls, South Dakota.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<DataBankList CompleteYN="Y">
<DataBank>
<DataBankName>ClinicalTrials.gov</DataBankName>
<AccessionNumberList>
<AccessionNumber>NCT00045032</AccessionNumber>
</AccessionNumberList>
</DataBank>
</DataBankList>
<PublicationTypeList>
<PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
</Article>
<MedlineJournalInfo>
<Country>United States</Country>
<MedlineTA>JAMA Oncol</MedlineTA>
<NlmUniqueID>101652861</NlmUniqueID>
<ISSNLinking>2374-2437</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D047628">Estrogen Receptor alpha</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C506487">estrogen receptor alpha, human</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 2.7.10.1</RegistryNumber>
<NameOfSubstance UI="C508053">ERBB2 protein, human</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>EC 2.7.10.1</RegistryNumber>
<NameOfSubstance UI="D018719">Receptor, ErbB-2</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>P188ANX8CK</RegistryNumber>
<NameOfSubstance UI="D000068878">Trastuzumab</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList>
<CommentsCorrections RefType="CommentIn">
<RefSource>JAMA Oncol. 2016 Aug 1;2(8):1047-8</RefSource>
<PMID Version="1">27099974</PMID>
</CommentsCorrections>
</CommentsCorrectionsList>
<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000970" MajorTopicYN="N">Antineoplastic Agents</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D001943" MajorTopicYN="N">Breast Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D002277" MajorTopicYN="N">Carcinoma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017024" MajorTopicYN="N">Chemotherapy, Adjuvant</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D018572" MajorTopicYN="N">Disease-Free Survival</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D047628" MajorTopicYN="N">Estrogen Receptor alpha</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D017404" MajorTopicYN="N">In Situ Hybridization, Fluorescence</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015999" MajorTopicYN="N">Multivariate Analysis</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D011379" MajorTopicYN="N">Prognosis</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D016016" MajorTopicYN="N">Proportional Hazards Models</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D012333" MajorTopicYN="N">RNA, Messenger</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
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<MeshHeading>
<DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018719" MajorTopicYN="N">Receptor, ErbB-2</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000068878" MajorTopicYN="N">Trastuzumab</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
</MeshHeadingList>
</MedlineCitation>
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<Year>2016</Year>
<Month>4</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline">
<Year>2017</Year>
<Month>1</Month>
<Day>31</Day>
<Hour>6</Hour>
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<PublicationStatus>ppublish</PublicationStatus>
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<list>
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<li>Allemagne</li>
<li>Australie</li>
<li>Belgique</li>
<li>France</li>
<li>Grèce</li>
<li>Italie</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
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<li>Attique (région)</li>
<li>Dakota du Sud</li>
<li>District de Kassel</li>
<li>Hesse (Land)</li>
<li>Illinois</li>
<li>Lombardie</li>
<li>Région de Bruxelles-Capitale</li>
</region>
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<li>Athènes</li>
<li>Bruxelles</li>
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<region name="Région de Bruxelles-Capitale">
<name sortKey="De Azambuja, Evandro" sort="De Azambuja, Evandro" uniqKey="De Azambuja E" first="Evandro" last="De Azambuja">Evandro De Azambuja</name>
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<name sortKey="Piccart, Martine J" sort="Piccart, Martine J" uniqKey="Piccart M" first="Martine J" last="Piccart">Martine J. Piccart</name>
<name sortKey="Sotiriou, Christos" sort="Sotiriou, Christos" uniqKey="Sotiriou C" first="Christos" last="Sotiriou">Christos Sotiriou</name>
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<region name="Lombardie">
<name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name>
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<region name="Hesse (Land)">
<name sortKey="Ruschoff, Josef" sort="Ruschoff, Josef" uniqKey="Ruschoff J" first="Josef" last="Rüschoff">Josef Rüschoff</name>
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<country name="Royaume-Uni">
<region name="Angleterre">
<name sortKey="Dowsett, Mitch" sort="Dowsett, Mitch" uniqKey="Dowsett M" first="Mitch" last="Dowsett">Mitch Dowsett</name>
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