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 : 001F81Effects 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 :
- JAMA oncology [ 2374-2445 ] ; 2016.
Descripteurs français
- KwdFr :
- ARN messager (métabolisme), Adulte, Adulte d'âge moyen, Analyse multivariée, Antinéoplasiques (usage thérapeutique), Carcinomes (métabolisme), Carcinomes (traitement médicamenteux), Essais contrôlés randomisés comme sujet, Femelle, Humains, Immunohistochimie, Modèles de hasards proportionnels, Pronostic, Récepteur ErbB-2 (génétique), Récepteur ErbB-2 (métabolisme), Récepteur alpha des oestrogènes (génétique), Récepteur alpha des oestrogènes (métabolisme), Survie sans rechute, Technique FISH, Traitement médicamenteux adjuvant, Trastuzumab (usage thérapeutique), Tumeurs du sein (métabolisme), Tumeurs du sein (traitement médicamenteux).
- MESH :
- génétique : Récepteur ErbB-2, Récepteur alpha des oestrogènes.
- métabolisme : ARN messager, Carcinomes, Récepteur ErbB-2, Récepteur alpha des oestrogènes, Tumeurs du sein.
- traitement médicamenteux : Carcinomes, Tumeurs du sein.
- usage thérapeutique : Antinéoplasiques, Trastuzumab.
- Adulte, Adulte d'âge moyen, Analyse multivariée, Essais contrôlés randomisés comme sujet, Femelle, Humains, Immunohistochimie, Modèles de hasards proportionnels, Pronostic, Survie sans rechute, Technique FISH, Traitement médicamenteux adjuvant.
English descriptors
- KwdEn :
- Adult, Antineoplastic Agents (therapeutic use), Breast Neoplasms (drug therapy), Breast Neoplasms (metabolism), Carcinoma (drug therapy), Carcinoma (metabolism), Chemotherapy, Adjuvant, Disease-Free Survival, Estrogen Receptor alpha (genetics), Estrogen Receptor alpha (metabolism), Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, RNA, Messenger (metabolism), Randomized Controlled Trials as Topic, Receptor, ErbB-2 (genetics), Receptor, ErbB-2 (metabolism), Trastuzumab (therapeutic use).
- MESH :
- chemical , genetics : Estrogen Receptor alpha, Receptor, ErbB-2.
- chemical , metabolism : Estrogen Receptor alpha, RNA, Messenger, Receptor, ErbB-2.
- chemical , therapeutic use : Antineoplastic Agents, Trastuzumab.
- drug therapy : Breast Neoplasms, Carcinoma.
- metabolism : Breast Neoplasms, Carcinoma.
- Adult, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Randomized Controlled Trials as Topic.
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:
- Allemagne, Australie, Belgique, France, Grèce, Italie, Royaume-Uni, États-Unis
- Angleterre, Attique (région), Dakota du Sud, District de Kassel, Hesse (Land), Illinois, Lombardie, Région de Bruxelles-Capitale
- Athènes, Bruxelles, Cassel (Hesse), Milan
- Université libre de Bruxelles
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Links to Exploration step
pubmed:27100299Le document en format XML
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<term>Breast Neoplasms (metabolism)</term>
<term>Carcinoma (drug therapy)</term>
<term>Carcinoma (metabolism)</term>
<term>Chemotherapy, Adjuvant</term>
<term>Disease-Free Survival</term>
<term>Estrogen Receptor alpha (genetics)</term>
<term>Estrogen Receptor alpha (metabolism)</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>
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<term>RNA, Messenger (metabolism)</term>
<term>Randomized Controlled Trials as Topic</term>
<term>Receptor, ErbB-2 (genetics)</term>
<term>Receptor, ErbB-2 (metabolism)</term>
<term>Trastuzumab (therapeutic use)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>ARN messager (métabolisme)</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Antinéoplasiques (usage thérapeutique)</term>
<term>Carcinomes (métabolisme)</term>
<term>Carcinomes (traitement médicamenteux)</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>Récepteur ErbB-2 (génétique)</term>
<term>Récepteur ErbB-2 (métabolisme)</term>
<term>Récepteur alpha des oestrogènes (génétique)</term>
<term>Récepteur alpha des oestrogènes (métabolisme)</term>
<term>Survie sans rechute</term>
<term>Technique FISH</term>
<term>Traitement médicamenteux adjuvant</term>
<term>Trastuzumab (usage thérapeutique)</term>
<term>Tumeurs du sein (métabolisme)</term>
<term>Tumeurs du sein (traitement médicamenteux)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><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>
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<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>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018572" MajorTopicYN="N">Disease-Free Survival</DescriptorName>
</MeshHeading>
<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>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016032" MajorTopicYN="N">Randomized Controlled Trials as Topic</DescriptorName>
</MeshHeading>
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<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>
<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2016</Year>
<Month>4</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
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<PubMedPubDate PubStatus="medline"><Year>2017</Year>
<Month>1</Month>
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<Hour>6</Hour>
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<affiliations><list><country><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>
<region><li>Angleterre</li>
<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>
<settlement><li>Athènes</li>
<li>Bruxelles</li>
<li>Cassel (Hesse)</li>
<li>Milan</li>
</settlement>
<orgName><li>Université libre de Bruxelles</li>
</orgName>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Loi, Sherene" sort="Loi, Sherene" uniqKey="Loi S" first="Sherene" last="Loi">Sherene Loi</name>
</noRegion>
</country>
<country name="Grèce"><region name="Attique (région)"><name sortKey="Dafni, Urania" sort="Dafni, Urania" uniqKey="Dafni U" first="Urania" last="Dafni">Urania Dafni</name>
</region>
<name sortKey="Karlis, Dimitris" sort="Karlis, Dimitris" uniqKey="Karlis D" first="Dimitris" last="Karlis">Dimitris Karlis</name>
<name sortKey="Polydoropoulou, Varvara" sort="Polydoropoulou, Varvara" uniqKey="Polydoropoulou V" first="Varvara" last="Polydoropoulou">Varvara Polydoropoulou</name>
</country>
<country name="États-Unis"><region name="Dakota du Sud"><name sortKey="Young, Brandon M" sort="Young, Brandon M" uniqKey="Young B" first="Brandon M" last="Young">Brandon M. Young</name>
</region>
<name sortKey="Leyland Jones, Brian" sort="Leyland Jones, Brian" uniqKey="Leyland Jones B" first="Brian" last="Leyland-Jones">Brian Leyland-Jones</name>
<name sortKey="Long, Bradley" sort="Long, Bradley" uniqKey="Long B" first="Bradley" last="Long">Bradley Long</name>
<name sortKey="Willis, Scooter" sort="Willis, Scooter" uniqKey="Willis S" first="Scooter" last="Willis">Scooter Willis</name>
</country>
<country name="Belgique"><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>
</region>
<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>
</country>
<country name="Italie"><region name="Lombardie"><name sortKey="Viale, Giuseppe" sort="Viale, Giuseppe" uniqKey="Viale G" first="Giuseppe" last="Viale">Giuseppe Viale</name>
</region>
</country>
<country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Ruschoff, Josef" sort="Ruschoff, Josef" uniqKey="Ruschoff J" first="Josef" last="Rüschoff">Josef Rüschoff</name>
</region>
</country>
<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Dowsett, Mitch" sort="Dowsett, Mitch" uniqKey="Dowsett M" first="Mitch" last="Dowsett">Mitch Dowsett</name>
</region>
</country>
<country name="France"><noRegion><name sortKey="Michiels, Stefan" sort="Michiels, Stefan" uniqKey="Michiels S" first="Stefan" last="Michiels">Stefan Michiels</name>
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</country>
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