Towards tailored breast cancer screening: Assessing the added value of 313-polygenic risk score and breast density in a Dutch screening cohort
BOADICEA is a multifactorial breast cancer risk prediction model that incorporates established risk factors, including polygenic risk scores (PRS) and mammographic breast density (BD). While extensively validated in high-risk populations, its performance in screening cohorts remains unclear. This study evaluates the clinical validity of BOADICEA in a population-based screening cohort.
We validated BOADICEA (v7.3.2) in the PRISMA cohort (n=82,200 women in the Dutch screening program) using a nested case-control design, including 318 cases and 771 controls. Five-year risks were calculated based on sub-models including age, “clinical” risk factors (personal hormonal, lifestyle, and disease history, along with family history up to second-degree relatives), rare pathogenic variants (PVs), BD (Volpara-based continuous and categorical), and 313-PRS. Model performance was assessed using discrimination (C-index), calibration (observed/expected ratios, slope, calibration plots), risk reclassification (Net Reclassification Index, NRI), and decision analysis (Net Benefit, NB).
| File | Description |
|---|---|
| 05_External_validation.Rmd | Validation of the BOADICEA model in the raw dataset. |
| 05_External_validation_imp.Rmd | Validation of the BOADICEA model in an imputed dataset. |
| 05_External_validation_DCIShg.Rmd | Validation of the BOADICEA model in the dataset including high grade DCIS as cases. |
| 05_External_validation_DCISall.Rmd | Validation of the BOADICEA model in the dataset including all DCIS as cases. |
| 05_External_validation_subg_Age.Rmd | Subgroup analysis by age. |
| 06_DCA_Simulation | Additional analysis and simulations conducted for assessing utility for decisions on screening intervals. |
| perf_functions.R | Functions to calculate model performance. |
Mary Ann E. Binuya
Netherlands Cancer Institute
m.binuya@nki.nl
| Author | Role | Description |
|---|---|---|
| Mary Ann Binuya | Author | Development and support |
| Renée Verdiesen | Author | Development and review |
| Jim Peters | Author | Development and review |
| Maartje Schreurs | Author | Review |
| Danielle van der Waal | Author | Review |
| Marjanka Schmidt | Author | Review |
| Mireille Broeders | Author | Review |