title: Breast cancer risk prediction using a clinical risk model and polygenic risk score.
abstract: Breast cancer risk assessment can inform the use of screening and prevention modalities. We investigated the performance of the Breast Cancer Surveillance Consortium (BCSC) risk model in combination with a polygenic risk score (PRS) comprised of 83 single nucleotide polymorphisms identified from genome-wide association studies. We conducted a nested case-control study of 486 cases and 495 matched controls within a screening cohort. The PRS was calculated using a Bayesian approach. The contributions of the PRS and variables in the BCSC model to breast cancer risk were tested using conditional logistic regression. Discriminatory accuracy of the models was compared using the area under the receiver operating characteristic curve (AUROC). Increasing quartiles of the PRS were positively associated with breast cancer risk, with OR 2.54 (95 % CI 1.69-3.82) for breast cancer in the highest versus lowest quartile. In a multivariable model, the PRS, family history, and breast density remained strong risk factors. The AUROC of the PRS was 0.60 (95 % CI 0.57-0.64), and an Asian-specific PRS had AUROC 0.64 (95 % CI 0.53-0.74). A combined model including the BCSC risk factors and PRS had better discrimination than the BCSC model (AUROC 0.65 versus 0.62, p = 0.01). The BCSC-PRS model classified 18 % of cases as high-risk (5-year risk ≥3 %), compared with 7 % using the BCSC model. The PRS improved discrimination of the BCSC risk model and classified more cases as high-risk. Further consideration of the PRS's role in decision-making around screening and prevention strategies is merited.
authors: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94143, USA. yiwey.shieh@ucsf.edu.
authors: Yiwey
authors: http://orcid.org/0000-0002-0159-7748
authors: Y
authors: Shieh
authors: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94143, USA.
authors: Donglei
authors: D
authors: Hu
authors: University of California, San Francisco, Box 1793, 550 16th Street, San Francisco, CA, 94158, USA.
authors: Lin
authors: L
authors: Ma
authors: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94143, USA.
authors: Scott
authors: S
authors: Huntsman
authors: Department of Economics, Applied Statistics, and International Business, New Mexico State University, MSC 3CQ, P.O. Box 30001, Las Cruces, NM, 88003, USA.
authors: Charlotte C
authors: CC
authors: Gard
authors: Department of Diagnostic Radiology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1350, Houston, TX, 77030, USA.
authors: Jessica W T
authors: JW
authors: Leung
authors: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94143, USA.
authors: Jeffrey A
authors: JA
authors: Tice
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, 200 First Street SW, Charlton Building 6-239, Rochester, MN, 55905, USA.
authors: Celine M
authors: CM
authors: Vachon
authors: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, Box 0560, 550 16th Street, 2nd Floor, San Francisco, CA, 94159, USA.
authors: Steven R
authors: SR
authors: Cummings
authors: Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, USA.|General Internal Medicine Section, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, Mailing Code 111A1, San Francisco, CA, 94121, USA.
authors: Karla
authors: K
authors: Kerlikowske
authors: Division of General Internal Medicine, Department of Medicine, University of California, San Francisco, Box 0320, 1545 Divisadero Street, San Francisco, CA, 94143, USA.
authors: Elad
authors: E
authors: Ziv
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001499:Bayes Theorem; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
keywords: Breast cancer; Cancer surveillance and screening; Risk assessment; Single nucleotide polymorphisms