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dc.contributor.authorGellert, Pen_US
dc.contributor.authorSegal, CVen_US
dc.contributor.authorGao, Qen_US
dc.contributor.authorLópez-Knowles, Een_US
dc.contributor.authorMartin, L-Aen_US
dc.contributor.authorDodson, Aen_US
dc.contributor.authorLi, Ten_US
dc.contributor.authorMiller, CAen_US
dc.contributor.authorLu, Cen_US
dc.contributor.authorMardis, ERen_US
dc.contributor.authorGillman, Aen_US
dc.contributor.authorMorden, Jen_US
dc.contributor.authorGraf, Men_US
dc.contributor.authorSidhu, Ken_US
dc.contributor.authorEvans, Aen_US
dc.contributor.authorShere, Men_US
dc.contributor.authorHolcombe, Cen_US
dc.contributor.authorMcIntosh, SAen_US
dc.contributor.authorBundred, Nen_US
dc.contributor.authorSkene, Aen_US
dc.contributor.authorMaxwell, Wen_US
dc.contributor.authorRobertson, Jen_US
dc.contributor.authorBliss, JMen_US
dc.contributor.authorSmith, Ien_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorPOETIC Trial Management Group and Trialistsen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2016-09-28T12:10:25Z
dc.date.issued2016-11-09en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/27827358en_US
dc.identifierncomms13294en_US
dc.identifier.citationNat Commun, 2016, 7 pp. 13294 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/139
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/ncomms13294en_US
dc.description.abstractPre-surgical studies allow study of the relationship between mutations and response of oestrogen receptor-positive (ER+) breast cancer to aromatase inhibitors (AIs) but have been limited to small biopsies. Here in phase I of this study, we perform exome sequencing on baseline, surgical core-cuts and blood from 60 patients (40 AI treated, 20 controls). In poor responders (based on Ki67 change), we find significantly more somatic mutations than good responders. Subclones exclusive to baseline or surgical cores occur in ∼30% of tumours. In phase II, we combine targeted sequencing on another 28 treated patients with phase I. We find six genes frequently mutated: PIK3CA, TP53, CDH1, MLL3, ABCA13 and FLG with 71% concordance between paired cores. TP53 mutations are associated with poor response. We conclude that multiple biopsies are essential for confident mutational profiling of ER+ breast cancer and TP53 mutations are associated with resistance to oestrogen deprivation therapy.en_US
dc.format.extent13294 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectAromatase Inhibitorsen_US
dc.subjectBiopsyen_US
dc.subjectBreasten_US
dc.subjectBreast Neoplasmsen_US
dc.subjectDNA Mutational Analysisen_US
dc.subjectDrug Resistance, Neoplasmen_US
dc.subjectEstrogensen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectKi-67 Antigenen_US
dc.subjectMiddle Ageden_US
dc.subjectMutationen_US
dc.subjectReceptors, Estrogenen_US
dc.subjectTreatment Outcomeen_US
dc.subjectTumor Suppressor Protein p53en_US
dc.subjectWhole Exome Sequencingen_US
dc.titleImpact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-09-19en_US
rioxxterms.versionofrecord10.1038/ncomms13294en_US
rioxxterms.licenseref.startdate2016-11-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNat Communen_US
pubs.notes12 monthsen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Endocrinology/Endocrinology (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished onlineen_US
pubs.volume7en_US
pubs.embargo.terms12 monthsen_US
icr.researchteamClinical Trials & Statistics Uniten_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen_US
dc.contributor.icrauthorMartin, Lesley-Annen_US
dc.contributor.icrauthorSmith, Ianen_US
dc.contributor.icrauthorMorden, James Peteren_US
dc.contributor.icrauthorGillman, Alexaen_US
dc.contributor.icrauthorBliss, Judithen_US
dc.contributor.icrauthorGao, Qiongen_US
dc.contributor.icrauthorLopez Knowles, Elenaen_US


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