Validation of the BOADICEA model in a prospective cohort of pathogenic variant carriers.

BACKGROUND

No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of PV carriers ascertained through clinical genetic centres.

METHODS

We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 and 1365 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information.

RESULTS

The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in or PV carriers. The full model identified 5.8%, 12.9% and 24.0% of PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options.

CONCLUSION

BOADICEA may be used to aid personalised cancer risk management and decision-making for and PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).