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dc.contributor.authorO'Leary, B
dc.contributor.authorHrebien, S
dc.contributor.authorMorden, JP
dc.contributor.authorBeaney, M
dc.contributor.authorFribbens, C
dc.contributor.authorHuang, X
dc.contributor.authorLiu, Y
dc.contributor.authorBartlett, CH
dc.contributor.authorKoehler, M
dc.contributor.authorCristofanilli, M
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorBliss, JM
dc.contributor.authorTurner, NC
dc.date.accessioned2018-02-13T12:42:31Z
dc.date.issued2018-03
dc.identifier.citationNature communications, 2018, 9 (1), pp. 896 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1050
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-018-03215-xen_US
dc.description.abstractCDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.
dc.formatElectronic
dc.format.extent896 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectPiperazines
dc.subjectPyridines
dc.subjectEstradiol
dc.subjectReceptors, Estrogen
dc.subjectAntineoplastic Agents
dc.subjectDisease-Free Survival
dc.subjectFemale
dc.subjectCyclin-Dependent Kinase 6
dc.subjectClass I Phosphatidylinositol 3-Kinases
dc.subjectCirculating Tumor DNA
dc.subjectFulvestrant
dc.titleEarly circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-01-29
rioxxterms.versionofrecord10.1038/s41467-018-03215-x
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-03en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
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/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
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/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.publication-statusPublished
pubs.volume9en_US
pubs.embargo.termsNot known
icr.researchteamMolecular Oncologyen_US
icr.researchteamClinical Trials & Statistics Uniten_US
dc.contributor.icrauthorHrebien, Sarahen
dc.contributor.icrauthorMorden, James Peteren
dc.contributor.icrauthorTurner, Nicholasen
dc.contributor.icrauthorO'Leary, Benjaminen
dc.contributor.icrauthorGarcia-Murillas, Isaacen
dc.contributor.icrauthorBliss, Judithen


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