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dc.contributor.authorLawler, K
dc.contributor.authorPapouli, E
dc.contributor.authorNaceur-Lombardelli, C
dc.contributor.authorMera, A
dc.contributor.authorOugham, K
dc.contributor.authorTutt, A
dc.contributor.authorKimbung, S
dc.contributor.authorHedenfalk, I
dc.contributor.authorZhan, J
dc.contributor.authorZhang, H
dc.contributor.authorBuus, R
dc.contributor.authorDowsett, M
dc.contributor.authorNg, T
dc.contributor.authorPinder, SE
dc.contributor.authorParker, P
dc.contributor.authorHolmberg, L
dc.contributor.authorGillett, CE
dc.contributor.authorGrigoriadis, A
dc.contributor.authorPurushotham, A
dc.date.accessioned2018-01-24T11:32:57Z
dc.date.issued2017-10-13
dc.identifier.citationBreast cancer research : BCR, 2017, 19 (1), pp. 113 - ?
dc.identifier.issn1465-5411
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1011
dc.identifier.eissn1465-542X
dc.identifier.doi10.1186/s13058-017-0881-y
dc.description.abstractMetastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are limited.A case-control design including 1357 primary breast cancers was used to study three distinct clinical patterns of metastasis, which occur within the first six months of metastatic disease: bone and visceral metasynchronous spread, bone-only, and visceral-only metastasis. Whole-genome expression profiles were obtained using whole genome (WG)-DASL assays from formalin-fixed paraffin-embedded (FFPE) samples. A systematic protocol was developed for handling FFPE samples together with stringent data quality controls to identify robust expression profiling data. A panel of published and novel gene sets were tested for association with these specific patterns of metastatic spread and odds ratios (ORs) were calculated.Metasynchronous metastasis to bone and viscera was found in all intrinsic breast cancer subtypes, while immunohistochemically (IHC)-defined receptor status and specific IntClust subgroups were risk factors for visceral-only or bone-only first metastases. Among gene modules, those related to proliferation increased the risk of metasynchronous metastasis (OR (95% CI) = 2.3 (1.1-4.8)) and visceral-only first metastasis (OR (95% CI) = 2.5 (1.2-5.1)) but not bone-only metastasis (OR (95% CI) = 0.97 (0.56-1.7)). A 21-gene module (BV) was identified in estrogen-receptor-positive breast cancers with metasynchronous metastasis to bone and viscera (area under the curve = 0.77), and its expression increased the risk of bone and visceral metasynchronous spread in this population. BV was further orthogonally validated with NanoString nCounter in primary breast cancers, and was reproducible in their matched lymph nodes metastases and an external cohort.This case-control study of WG-DASL global expression profiles from FFPE tumour samples, after careful quality control and RNA selection, revealed that gene modules in the primary tumour have differing risks for clinical patterns of metasynchronous first metastases. Moreover, a novel gene module was identified as a putative risk factor for metasynchronous bone and visceral first metastatic spread, with potential implications for disease monitoring and treatment planning.
dc.formatElectronic
dc.format.extent113 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectBreast Neoplasms
dc.subjectLymphatic Metastasis
dc.subjectFormaldehyde
dc.subjectNeoplasm Proteins
dc.subjectPrognosis
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectParaffin Embedding
dc.subjectRisk Factors
dc.subjectCase-Control Studies
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectOrgans at Risk
dc.titleGene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study.
dc.typeJournal Article
dcterms.dateAccepted2017-07-12
rioxxterms.versionofrecord10.1186/s13058-017-0881-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-10-13
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBreast cancer research : BCR
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/Endocrinology
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.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/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.publication-statusPublished
pubs.volume19
pubs.embargo.termsNot known
icr.researchteamEndocrinologyen_US
dc.contributor.icrauthorDowsett, Mitchen
dc.contributor.icrauthorTutt, Andrewen
dc.contributor.icrauthorBuus, Richarden


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