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dc.contributor.authorGellert, P
dc.contributor.authorSegal, CV
dc.contributor.authorGao, Q
dc.contributor.authorLópez-Knowles, E
dc.contributor.authorMartin, L-A
dc.contributor.authorDodson, A
dc.contributor.authorLi, T
dc.contributor.authorMiller, CA
dc.contributor.authorLu, C
dc.contributor.authorMardis, ER
dc.contributor.authorGillman, A
dc.contributor.authorMorden, J
dc.contributor.authorGraf, M
dc.contributor.authorSidhu, K
dc.contributor.authorEvans, A
dc.contributor.authorShere, M
dc.contributor.authorHolcombe, C
dc.contributor.authorMcIntosh, SA
dc.contributor.authorBundred, N
dc.contributor.authorSkene, A
dc.contributor.authorMaxwell, W
dc.contributor.authorRobertson, J
dc.contributor.authorBliss, JM
dc.contributor.authorSmith, I
dc.contributor.authorDowsett, M
dc.contributor.authorPOETIC Trial Management Group and Trialists
dc.date.accessioned2016-09-28T12:10:25Z
dc.date.issued2016-11-09
dc.identifier.citationNature communications, 2016, 7 pp. 13294 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/139
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/ncomms13294
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.
dc.formatElectronic
dc.format.extent13294 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPOETIC Trial Management Group and Trialists
dc.subjectBreast
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectKi-67 Antigen
dc.subjectReceptors, Estrogen
dc.subjectAntineoplastic Agents
dc.subjectAromatase Inhibitors
dc.subjectEstrogens
dc.subjectBiopsy
dc.subjectTreatment Outcome
dc.subjectDNA Mutational Analysis
dc.subjectDrug Resistance, Neoplasm
dc.subjectMutation
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectTumor Suppressor Protein p53
dc.subjectWhole Exome Sequencing
dc.titleImpact of mutational profiles on response of primary oestrogen receptor-positive breast cancers to oestrogen deprivation.
dc.typeJournal Article
dcterms.dateAccepted2016-09-19
rioxxterms.versionofrecord10.1038/ncomms13294
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-11-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.notes12 months
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.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
pubs.volume7
pubs.embargo.terms12 months
icr.researchteamClinical Trials & Statistics Uniten_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorSmith, Ianen
dc.contributor.icrauthorMorden, James Peteren
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorMartin, Lesley-Annen
dc.contributor.icrauthorGillman, Alexaen
dc.contributor.icrauthorBliss, Judithen
dc.contributor.icrauthorGao, Qiongen
dc.contributor.icrauthorLopez Knowles, Elenaen


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