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dc.contributor.authorCopson, ERen_US
dc.contributor.authorMaishman, TCen_US
dc.contributor.authorTapper, WJen_US
dc.contributor.authorCutress, RIen_US
dc.contributor.authorGreville-Heygate, Sen_US
dc.contributor.authorAltman, DGen_US
dc.contributor.authorEccles, Ben_US
dc.contributor.authorGerty, Sen_US
dc.contributor.authorDurcan, LTen_US
dc.contributor.authorJones, Len_US
dc.contributor.authorEvans, DGen_US
dc.contributor.authorThompson, AMen_US
dc.contributor.authorPharoah, Pen_US
dc.contributor.authorEaston, DFen_US
dc.contributor.authorDunning, AMen_US
dc.contributor.authorHanby, Aen_US
dc.contributor.authorLakhani, Sen_US
dc.contributor.authorEeles, Ren_US
dc.contributor.authorGilbert, FJen_US
dc.contributor.authorHamed, Hen_US
dc.contributor.authorHodgson, Sen_US
dc.contributor.authorSimmonds, Pen_US
dc.contributor.authorStanton, Len_US
dc.contributor.authorEccles, DMen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-11-26T14:38:03Z
dc.date.issued2018-02en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29337092en_US
dc.identifierS1470-2045(17)30891-4en_US
dc.identifier.citationLancet Oncol, 2018, 19 (2), pp. 169 - 180en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2953
dc.identifier.eissn1474-5488en_US
dc.identifier.doi10.1016/S1470-2045(17)30891-4en_US
dc.description.abstractBACKGROUND: Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer. METHODS: We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing. FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0-9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5-98·4] vs 96·6% [95·8-97·3]; at 5 years: 83·8% [79·3-87·5] vs 85·0% [83·5-86·4]; at 10 years: 73·4% [67·4-78·5] vs 70·1% [67·7-72·3]; hazard ratio [HR] 0·96 [95% CI 0·76-1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89-97] vs 91% [88-94]; HR 0·59 [95% CI 0·35-0·99]; p=0·047) but not 5 years (81% [73-87] vs 74% [70-78]; HR 1·13 [0·70-1·84]; p=0·62) or 10 years (72% [62-80] vs 69% [63-74]; HR 2·12 [0·82-5·49]; p= 0·12). INTERPRETATION: Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences. FUNDING: Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.en_US
dc.format.extent169 - 180en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAdulten_US
dc.subjectAge Factorsen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectCohort Studiesen_US
dc.subjectCombined Modality Therapyen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectFemaleen_US
dc.subjectGenes, BRCA1en_US
dc.subjectGenes, BRCA2en_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGerm-Line Mutationen_US
dc.subjectHumansen_US
dc.subjectMultivariate Analysisen_US
dc.subjectPatient Outcome Assessmenten_US
dc.subjectPrognosisen_US
dc.subjectProportional Hazards Modelsen_US
dc.subjectProspective Studiesen_US
dc.subjectSurvival Analysisen_US
dc.subjectTriple Negative Breast Neoplasmsen_US
dc.subjectUnited Kingdomen_US
dc.subjectYoung Adulten_US
dc.titleGermline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-11-08en_US
rioxxterms.versionofrecord10.1016/S1470-2045(17)30891-4en_US
rioxxterms.licenseref.startdate2018-02en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfLancet Oncolen_US
pubs.issue2en_US
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/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublisheden_US
pubs.volume19en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden_US


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