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dc.contributor.authorFribbens, Cen_US
dc.contributor.authorO'Leary, Ben_US
dc.contributor.authorKilburn, Len_US
dc.contributor.authorHrebien, Sen_US
dc.contributor.authorGarcia-Murillas, Ien_US
dc.contributor.authorBeaney, Men_US
dc.contributor.authorCristofanilli, Men_US
dc.contributor.authorAndre, Fen_US
dc.contributor.authorLoi, Sen_US
dc.contributor.authorLoibl, Sen_US
dc.contributor.authorJiang, Jen_US
dc.contributor.authorBartlett, CHen_US
dc.contributor.authorKoehler, Men_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorBliss, JMen_US
dc.contributor.authorJohnston, SRen_US
dc.contributor.authorTurner, NCen_US
dc.date.accessioned2016-11-24T15:15:32Z
dc.date.issued2016-09en_US
dc.identifier.citationJournal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (25), pp. 2961 - 2968en_US
dc.identifier.issn0732-183Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/305
dc.identifier.eissn1527-7755en_US
dc.identifier.doi10.1200/jco.2016.67.3061en_US
dc.description.abstractESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer.In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction.In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001).ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.en_US
dc.formatPrint-Electronicen_US
dc.format.extent2961 - 2968en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.isreplacedbyinternal/510
dc.relation.isreplacedbyhttps://repository.icr.ac.uk/handle/internal/510
dc.titlePlasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1200/jco.2016.67.3061en_US
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
rioxxterms.licenseref.startdate2016-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfJournal of clinical oncology : official journal of the American Society of Clinical Oncologyen_US
pubs.issue25en_US
pubs.notes6 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/Breast Cancer Research/Molecular Oncology
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/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.volume34en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamMolecular Oncologyen_US
icr.researchteamClinical Trials & Statistics Uniten_US
icr.researchteamEndocrinologyen_US


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