Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/21827
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dc.contributor.authorLeal, Mariana F-
dc.contributor.authorHaynes, Benjamin P-
dc.contributor.authorSchuster, Eugene F-
dc.contributor.authorYeo, Belinda-
dc.contributor.authorAfentakis, Maria-
dc.contributor.authorZabaglo, Lila-
dc.contributor.authorMartins, Vera-
dc.contributor.authorBuus, Richard-
dc.contributor.authorDodson, Andrew-
dc.contributor.authorCheang, Maggie C U-
dc.contributor.authorSmith, Ian E-
dc.contributor.authorMartin, Lesley-Ann-
dc.contributor.authorDowsett, Mitch-
dc.date2019-09-23-
dc.date.accessioned2019-09-29T23:26:18Z-
dc.date.available2019-09-29T23:26:18Z-
dc.date.issued2019-09-23-
dc.identifier.citationClinical Cancer Research 2019; online first: 23 September-
dc.identifier.issn1078-0432-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/21827-
dc.description.abstractTo 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. 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. 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. 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.language.isoeng-
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-
dc.identifier.journaltitleClinical Cancer Research-
dc.identifier.affiliationEndocrinology, Institute of Cancer Research-
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.affiliationAcademic Department of Biochemistry, The Royal Marsden Hospital/The Institute of Cancer Research-
dc.identifier.affiliationRalph Lauren Centre for Breast Cancer Research, Institute of Cancer Research-
dc.identifier.affiliationRalph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital-
dc.identifier.affiliationBreast Cancer Research, Institute of Cancer Research-
dc.identifier.affiliationDepartment of Academic Biochemistry, Royal Marsden Hospital-
dc.identifier.affiliationClinical Trials and Statistics Unit (ICR-CTSU), Institute of Cancer Research-
dc.identifier.affiliationMedicine- Breast Unit, The Royal Marsden Hospital/The Institute of Cancer Research-
dc.identifier.affiliationThe Breast Cancer Now Toby Robins Breast Cancer Research Centre, Institute of Cancer Research-
dc.identifier.affiliationRalph Lauren Centre for Breast Cancer Research, Royal Marsden Hospital-
dc.identifier.doi10.1158/1078-0432.CCR-19-1129-
dc.identifier.orcid0000-0003-4375-2563-
dc.identifier.orcid0000-0002-3386-3465-
dc.identifier.orcid0000-0001-5718-2501-
dc.identifier.orcid0000-0002-7606-4161-
dc.identifier.orcid0000-0002-9218-9917-
dc.identifier.pubmedid31548345-
dc.type.austinJournal Article-
local.name.researcherYeo, Belinda
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
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