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dc.contributor.authorBarry, Pen_US
dc.contributor.authorVatsiou, Aen_US
dc.contributor.authorSpiteri, Ien_US
dc.contributor.authorNichol, Den_US
dc.contributor.authorCresswell, GDen_US
dc.contributor.authorAcar, Aen_US
dc.contributor.authorTrahearn, Nen_US
dc.contributor.authorHrebien, Sen_US
dc.contributor.authorGarcia-Murillas, Ien_US
dc.contributor.authorChkhaidze, Ken_US
dc.contributor.authorErmini, Len_US
dc.contributor.authorHuntingford, ISen_US
dc.contributor.authorCottom, Hen_US
dc.contributor.authorZabaglo, Len_US
dc.contributor.authorKoelble, Ken_US
dc.contributor.authorKhalique, Sen_US
dc.contributor.authorRusby, JEen_US
dc.contributor.authorMuscara, Fen_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorMaley, CCen_US
dc.contributor.authorNatrajan, Ren_US
dc.contributor.authorYuan, Yen_US
dc.contributor.authorSchiavon, Gen_US
dc.contributor.authorTurner, Nen_US
dc.contributor.authorSottoriva, Aen_US
dc.date.accessioned2018-07-04T13:02:12Z
dc.date.accessioned2020-02-24T11:14:11Z
dc.date.issued2018-10en_US
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (19), pp. 4763 - 4770en_US
dc.identifier.issn1078-0432en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3516
dc.identifier.doi10.1158/1078-0432.ccr-17-3374en_US
dc.description.abstractPurpose: The most significant prognostic factor in early breast cancer is lymph node involvement. This stage between localized and systemic disease is key to understanding breast cancer progression; however, our knowledge of the evolution of lymph node malignant invasion remains limited, as most currently available data are derived from primary tumors.Experimental Design: In 11 patients with treatment-naïve node-positive early breast cancer without clinical evidence of distant metastasis, we investigated lymph node evolution using spatial multiregion sequencing (n = 78 samples) of primary and lymph node deposits and genomic profiling of matched longitudinal circulating tumor DNA (ctDNA).Results: Linear evolution from primary to lymph node was rare (1/11), whereas the majority of cases displayed either early divergence between primary and nodes (4/11) or no detectable divergence (6/11), where both primary and nodal cells belonged to a single recent expansion of a metastatic clone. Divergence of metastatic subclones was driven in part by APOBEC. Longitudinal ctDNA samples from 2 of 7 subjects with evaluable plasma taken perioperatively reflected the two major evolutionary patterns and demonstrate that private mutations can be detected even from early metastatic nodal deposits. Moreover, node removal resulted in disappearance of private lymph node mutations in ctDNA.Conclusions: This study sheds new light on a crucial evolutionary step in the natural history of breast cancer, demonstrating early establishment of axillary lymph node metastasis in a substantial proportion of patients. Clin Cancer Res; 24(19); 4763-70. ©2018 AACR.en_US
dc.formatPrint-Electronicen_US
dc.format.extent4763 - 4770en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1973
dc.relation.replacesinternal/1973
dc.relation.replacesinternal/1868
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/1868
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAxillaen_US
dc.subjectLymph Nodesen_US
dc.subjectHumansen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectLymphatic Metastasisen_US
dc.subjectNeoplasm Proteinsen_US
dc.subjectNeoplasm Stagingen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectClonal Evolutionen_US
dc.subjectCirculating Tumor DNAen_US
dc.titleThe Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-06-05en_US
rioxxterms.versionofrecord10.1158/1078-0432.ccr-17-3374en_US
rioxxterms.licenseref.startdate2018-10en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Researchen_US
pubs.issue19en_US
pubs.merge-frominternal/1868
pubs.merge-fromhttps://repository.icr.ac.uk/handle/internal/1868
pubs.notesNot knownen_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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
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/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Functional Genomics
pubs.publication-statusPublisheden_US
pubs.volume24en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Oncologyen_US
icr.researchteamComputational Pathology & Integrated Genomicsen_US
icr.researchteamEndocrinologyen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
icr.researchteamFunctional Genomicsen_US
dc.contributor.icrauthorGarcia-Murillas, Isaacen_US
dc.contributor.icrauthorRusby, Jenniferen_US
dc.contributor.icrauthorNatrajan, Rachaelen_US
dc.contributor.icrauthorTurner, Nicholasen_US
dc.contributor.icrauthorDowsett, Mitchen_US
dc.contributor.icrauthorYuan, Yinyinen_US
dc.contributor.icrauthorHrebien, Sarahen_US
dc.contributor.icrauthorSottoriva, Andreaen_US
dc.contributor.icrauthorKhalique, Sairaen_US
dc.contributor.icrauthorSpiteri Sagastume, Mariaen_US
dc.contributor.icrauthorLise, Stefanoen_US
dc.contributor.icrauthorAcar, Ahmeten_US
dc.contributor.icrauthorCresswell, Georgeen_US


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