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dc.contributor.authorPal Choudhury, Parichoy
dc.contributor.authorBrook, Mark N.
dc.contributor.authorHurson, Amber N.
dc.contributor.authorLee, Andrew
dc.contributor.authorMulder, Charlotta V.
dc.contributor.authorCoulson, Penny
dc.contributor.authorSchoemaker, Minouk J.
dc.contributor.authorJones, Michael E.
dc.contributor.authorSwerdlow, Anthony J.
dc.contributor.authorChatterjee, Nilanjan
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorGarcia-Closas, Montserrat
dc.description.abstractAbstract: Background: The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS. Methods: Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23–75 years from the Generations Study. Results: The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 − 1.86) for women younger than 50 years and 1.09 (0.66 − 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 − 2.92) for younger and 1.73 (1.03 − 2.90) for older women. Conclusion: The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.subjectShort Report
dc.subjectAbsolute risk
dc.subjectBreast cancer
dc.subjectModel validation
dc.subjectProspective cohort
dc.subjectRisk prediction
dc.titleComparative validation of the BOADICEA and Tyrer-Cuzick breast cancer risk models incorporating classical risk factors and polygenic risk in a population-based prospective cohort of women of European ancestry
prism.publicationNameBreast Cancer Research
pubs.funder-project-idHorizon 2020 Framework Programme (633784)
pubs.funder-project-idInstitute of Cancer Research (Generation Study funding)
pubs.funder-project-idDivision of Cancer Epidemiology and Genetics, National Cancer Institute (Intramural Research Program, Intramural Research Program, T32-CA057726)
pubs.funder-project-idPatient-Centered Outcomes Research Institute (US) (ME1602-34530)

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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)