dc.contributor.author | Barry, P | |
dc.contributor.author | Vatsiou, A | |
dc.contributor.author | Spiteri, I | |
dc.contributor.author | Nichol, D | |
dc.contributor.author | Cresswell, GD | |
dc.contributor.author | Acar, A | |
dc.contributor.author | Trahearn, N | |
dc.contributor.author | Hrebien, S | |
dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Chkhaidze, K | |
dc.contributor.author | Ermini, L | |
dc.contributor.author | Huntingford, IS | |
dc.contributor.author | Cottom, H | |
dc.contributor.author | Zabaglo, L | |
dc.contributor.author | Koelble, K | |
dc.contributor.author | Khalique, S | |
dc.contributor.author | Rusby, JE | |
dc.contributor.author | Muscara, F | |
dc.contributor.author | Dowsett, M | |
dc.contributor.author | Maley, CC | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Yuan, Y | |
dc.contributor.author | Schiavon, G | |
dc.contributor.author | Turner, N | |
dc.contributor.author | Sottoriva, A | |
dc.date.accessioned | 2018-07-04T13:02:12Z | |
dc.date.accessioned | 2020-02-24T11:14:11Z | |
dc.date.issued | 2018-02-01 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (19), pp. 4763 - 4770 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3516 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-17-3374 | |
dc.description.abstract | Purpose: 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.format | Print-Electronic | |
dc.format.extent | 4763 - 4770 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGER | |
dc.relation.replaces | https://repository.icr.ac.uk/handle/internal/1973 | |
dc.relation.replaces | internal/1973 | |
dc.relation.replaces | internal/1868 | |
dc.relation.replaces | https://repository.icr.ac.uk/handle/internal/1868 | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Axilla | |
dc.subject | Lymph Nodes | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Lymphatic Metastasis | |
dc.subject | Neoplasm Proteins | |
dc.subject | Neoplasm Staging | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Clonal Evolution | |
dc.subject | Circulating Tumor DNA | |
dc.title | The Spatiotemporal Evolution of Lymph Node Spread in Early Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-06-05 | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-17-3374 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 19 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 24 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Computational Pathology & Integrated Genomics | |
icr.researchteam | Endocrinology | |
icr.researchteam | Evolutionary Genomics & Modelling | |
icr.researchteam | Functional Genomics | |
dc.contributor.icrauthor | Spiteri Sagastume, Maria | |
dc.contributor.icrauthor | Cresswell, George | |
dc.contributor.icrauthor | Acar, Ahmet | |
dc.contributor.icrauthor | Price, Sarah | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Chkhaidze, Ketevan | |
dc.contributor.icrauthor | Natrajan, Rachael | |
dc.contributor.icrauthor | Yuan, Yinyin | |
dc.contributor.icrauthor | Turner, Nicholas | |
dc.contributor.icrauthor | Sottoriva, Andrea | |