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dc.contributor.authorKuchenbaecker, KB
dc.contributor.authorHopper, JL
dc.contributor.authorBarnes, DR
dc.contributor.authorPhillips, K-A
dc.contributor.authorMooij, TM
dc.contributor.authorRoos-Blom, M-J
dc.contributor.authorJervis, S
dc.contributor.authorvan Leeuwen, FE
dc.contributor.authorMilne, RL
dc.contributor.authorAndrieu, N
dc.contributor.authorGoldgar, DE
dc.contributor.authorTerry, MB
dc.contributor.authorRookus, MA
dc.contributor.authorEaston, DF
dc.contributor.authorAntoniou, AC
dc.contributor.authorBRCA1 and BRCA2 Cohort Consortium
dc.contributor.authorMcGuffog, L
dc.contributor.authorEvans, DG
dc.contributor.authorBarrowdale, D
dc.contributor.authorFrost, D
dc.contributor.authorAdlard, J
dc.contributor.authorOng, K-R
dc.contributor.authorIzatt, L
dc.contributor.authorTischkowitz, M
dc.contributor.authorEeles, R
dc.contributor.authorDavidson, R
dc.contributor.authorHodgson, S
dc.contributor.authorEllis, S
dc.contributor.authorNogues, C
dc.contributor.authorLasset, C
dc.contributor.authorStoppa-Lyonnet, D
dc.contributor.authorFricker, J-P
dc.contributor.authorFaivre, L
dc.contributor.authorBerthet, P
dc.contributor.authorHooning, MJ
dc.contributor.authorvan der Kolk, LE
dc.contributor.authorKets, CM
dc.contributor.authorAdank, MA
dc.contributor.authorJohn, EM
dc.contributor.authorChung, WK
dc.contributor.authorAndrulis, IL
dc.contributor.authorSouthey, M
dc.contributor.authorDaly, MB
dc.contributor.authorBuys, SS
dc.contributor.authorOsorio, A
dc.contributor.authorEngel, C
dc.contributor.authorKast, K
dc.contributor.authorSchmutzler, RK
dc.contributor.authorCaldes, T
dc.contributor.authorJakubowska, A
dc.contributor.authorSimard, J
dc.contributor.authorFriedlander, ML
dc.contributor.authorMcLachlan, S-A
dc.contributor.authorMachackova, E
dc.contributor.authorForetova, L
dc.contributor.authorTan, YY
dc.contributor.authorSinger, CF
dc.contributor.authorOlah, E
dc.contributor.authorGerdes, A-M
dc.contributor.authorArver, B
dc.contributor.authorOlsson, H
dc.date.accessioned2017-08-02T10:11:16Z
dc.date.issued2017-06
dc.identifier.citationJAMA, 2017, 317 (23), pp. 2402 - 2416
dc.identifier.issn0098-7484
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/753
dc.identifier.eissn1538-3598
dc.identifier.doi10.1001/jama.2017.7112
dc.description.abstractImportance The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates.Objectives To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location.Design, setting, and participants Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years.Exposures BRCA1/2 mutations, family cancer history, and mutation location.Main outcomes and measures Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer.Results Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for ≥2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk was higher if mutations were located outside vs within the regions bounded by positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001).Conclusions and relevance These findings provide estimates of cancer risk based on BRCA1 and BRCA2 mutation carrier status using prospective data collection and demonstrate the potential importance of family history and mutation location in risk assessment.
dc.formatPrint
dc.format.extent2402 - 2416
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectBRCA1 and BRCA2 Cohort Consortium
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectOvarian Neoplasms
dc.subjectNeoplasms, Second Primary
dc.subjectIncidence
dc.subjectRisk Assessment
dc.subjectProspective Studies
dc.subjectFamily
dc.subjectAge Factors
dc.subjectAge Distribution
dc.subjectMutation
dc.subjectGenes, BRCA1
dc.subjectGenes, BRCA2
dc.subjectTime Factors
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.titleRisks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.
dc.typeJournal Article
dcterms.dateAccepted2017-05-18
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1001/jama.2017.7112
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJAMA
pubs.issue23
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/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.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-statusPublished
pubs.volume317
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden


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