Show simple item record

dc.contributor.authorBarry, P
dc.contributor.authorVatsiou, A
dc.contributor.authorSpiteri, I
dc.contributor.authorNichol, D
dc.contributor.authorCresswell, GD
dc.contributor.authorAcar, A
dc.contributor.authorTrahearn, N
dc.contributor.authorHrebien, S
dc.contributor.authorGarcia-Murillas, I
dc.contributor.authorChkhaidze, K
dc.contributor.authorErmini, L
dc.contributor.authorHuntingford, IS
dc.contributor.authorCottom, H
dc.contributor.authorZabaglo, L
dc.contributor.authorKoelble, K
dc.contributor.authorKhalique, S
dc.contributor.authorRusby, JE
dc.contributor.authorMuscara, F
dc.contributor.authorDowsett, M
dc.contributor.authorMaley, CC
dc.contributor.authorNatrajan, R
dc.contributor.authorYuan, Y
dc.contributor.authorSchiavon, G
dc.contributor.authorTurner, N
dc.contributor.authorSottoriva, A
dc.date.accessioned2018-07-04T13:02:12Z
dc.date.accessioned2020-02-24T11:14:11Z
dc.date.issued2018-02-01
dc.identifier.citationClinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (19), pp. 4763 - 4770
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3516
dc.identifier.eissn1557-3265
dc.identifier.doi10.1158/1078-0432.ccr-17-3374
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.
dc.formatPrint-Electronic
dc.format.extent4763 - 4770
dc.languageeng
dc.language.isoeng
dc.publisherSPRINGER
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.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAxilla
dc.subjectLymph Nodes
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectNeoplasm Proteins
dc.subjectNeoplasm Staging
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectClonal Evolution
dc.subjectCirculating Tumor DNA
dc.titleThe Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer.
dc.typeJournal Article
dcterms.dateAccepted2018-06-05
rioxxterms.versionofrecord10.1158/1078-0432.ccr-17-3374
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClinical cancer research : an official journal of the American Association for Cancer Research
pubs.issue19
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/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.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-statusPublished
pubs.volume24
pubs.embargo.termsNot known
icr.researchteamMolecular Oncology
icr.researchteamComputational Pathology & Integrated Genomics
icr.researchteamEndocrinology
icr.researchteamEvolutionary Genomics & Modelling
icr.researchteamFunctional Genomics
dc.contributor.icrauthorSpiteri Sagastume, Maria
dc.contributor.icrauthorCresswell, George
dc.contributor.icrauthorAcar, Ahmet
dc.contributor.icrauthorPrice, Sarah
dc.contributor.icrauthorGarcia-Murillas, Isaac
dc.contributor.icrauthorChkhaidze, Ketevan
dc.contributor.icrauthorNatrajan, Rachael
dc.contributor.icrauthorYuan, Yinyin
dc.contributor.icrauthorTurner, Nicholas
dc.contributor.icrauthorSottoriva, Andrea


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following collection(s)

Show simple item record

https://creativecommons.org/licenses/by/4.0
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0