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dc.contributor.authorLeal, MF
dc.contributor.authorHaynes, BP
dc.contributor.authorSchuster, EF
dc.contributor.authorYeo, B
dc.contributor.authorAfentakis, M
dc.contributor.authorZabaglo, L
dc.contributor.authorMartins, V
dc.contributor.authorBuus, R
dc.contributor.authorDodson, A
dc.contributor.authorCheang, MCU
dc.contributor.authorSmith, IE
dc.contributor.authorMartin, L-A
dc.contributor.authorDowsett, M
dc.coverage.spatialUnited States
dc.date.accessioned2019-10-14T08:48:50Z
dc.date.issued2019-09-23
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31548345
dc.identifier1078-0432.CCR-19-1129
dc.identifier.citationClin Cancer Res, 2019
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3380
dc.identifier.doi10.1158/1078-0432.CCR-19-1129
dc.description.abstractPURPOSE: To investigate the presence of ESR1 mutation in primary oestrogen-receptor positive breast cancer (ER+BC) treated with extended (>4 weeks) neoadjuvant (pre-surgical) aromatase inhibitor (NAI) therapy and to identify patients who may gain less benefit from aromatase inhibition (AI) alone based upon on-treatment changes in gene expression. EXPERIMENTAL DESIGN: We evaluated ER, progesterone receptor and Ki67 by immunostaining, ESR1 mutations by droplet-digital-PCR and expression of over 800 key BC genes in paired pre- and post-NAI tumour samples from 87 ER+BC patients. RESULTS: Cell proliferation and oestrogen-regulated genes (ERGs) remained suppressed in most tumours indicative of persistent response to NAI. Enrichment of ESR1 mutations was found in five tumours and predominantly in patients receiving therapy for >6 months. ESR1 mutant tumours showed increased expression of ESR1-transcript and limited suppression of ERGs and proliferation associated genes in response to NAI. ESR1 wild-type tumours with high residual proliferation (Ki67r≥10%; 15/87 tumours) showed lower ESR1/ER expression pre- and post-therapy and lower ERGs Tumours with ESR1 mutations or Ki67r≥10% showed less inhibition of oestrogen-response, cell-cycle and E2F-target genes. CONCLUSION: Ligand-independent ER-signalling, as a result of ESR1 mutation or reduced ER-dependence, identified after extended NAI therapy, can guide early selection of patients who would benefit from combination therapy.
dc.languageeng
dc.language.isoeng
dc.relation.isreplacedbyinternal/3438
dc.relation.isreplacedbyhttps://repository.icr.ac.uk/handle/internal/3438
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleEarly enrichment of ESR1 mutations and the impact on gene expression in pre-surgical primary breast cancer treated with aromatase inhibitors.
dc.typeJournal Article
dcterms.dateAccepted2019-09-09
rioxxterms.versionofrecord10.1158/1078-0432.CCR-19-1129
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-09-23
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClin Cancer Res
pubs.notesNot known
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/Genomic Analysis – Clinical Trials
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/Genomic Analysis – Clinical Trials
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 online
pubs.embargo.termsNot known
icr.researchteamGenomic Analysis – Clinical Trialsen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorSmith, Ianen
dc.contributor.icrauthorBuus, Richarden
dc.contributor.icrauthorMartin, Lesley-Annen
dc.contributor.icrauthorCheang, Chonen
dc.contributor.icrauthorDowsett, Mitchen


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