Comparative 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

Breast Cancer Research

Nilanjan Chatterjee¹  Antonis C. Antoniou²  Andrew Lee²  Parichoy Pal Choudhury³  Charlotta V. Mulder³  Montserrat Garcia-Closas³  Amber N. Hurson⁴  Mark N. Brook⁵  Penny Coulson⁵  Michael E. Jones⁵  Minouk J. Schoemaker⁵  Anthony J. Swerdlow⁶ 

[1] Department of Biostatistics, The Johns Hopkins University, Baltimore, MD, USA;Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK;Division of Cancer Epidemiology and Genetics, National Cancer Institute of Health, 9609 Medical Center Drive 7E-342, 20850, Rockville, MD, USA;Division of Cancer Epidemiology and Genetics, National Cancer Institute of Health, 9609 Medical Center Drive 7E-342, 20850, Rockville, MD, USA;Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK;Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK;Division of Breast Cancer Research, The Institute of Cancer Research, London, UK;

关键词: Absolute risk;    BOADICEA;    Breast cancer;    IBIS;    Model validation;    Prospective cohort;    Risk prediction;    Tyrer-Cuzick;   

DOI  :  10.1186/s13058-021-01399-7

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsCalibration 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.ResultsThe 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.ConclusionThe 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.

【 授权许可】

CC BY