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  • Validation of the BOADICEA model in a prospective cohort of<i>BRCA1/2</i>pathogenic variant carriers

Validation of the BOADICEA model in a prospective cohort of<i>BRCA1/2</i>pathogenic variant carriers

1 août 2024Journal of Medical Genetics

DOI : 10.1136/jmg-2024-109943

Auteurs

Xin Yang, Thea M Mooij, Goska Leslie, Lorenzo Ficorella, Nadine Andrieu, Karin Kast, Christian F. Singer, Anna Jakubowska, Carla H van Gils, Yen Y Tan, Christoph Engel, Muriel A Adank, Christi J van Asperen, Margreet G E M Ausems, Pascaline Berthet, , Margriet J Collee, Jackie A Cook, Jacqueline Eason, Karin Y van Spaendonck-Zwarts, D. Gareth Evans, Encarna B Gómez García, Helen Hanson, Louise Izatt, Zoe Kemp, Fiona Lalloo, Christine Lasset, Fabienne Lesueur, Hannah Musgrave, Sophie Nambot, Catherine Noguès, Jan C Oosterwijk, Dominique Stoppa-lyonnet, Marc Tischkowitz, Vishakha Tripathi, Marijke R Wevers, Emily Zhao, Flora E van Leeuwen, Marjanka K Schmidt, Douglas F Easton, Matti A Rookus, Antonis C Antoniou

Résumé

Background

No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically inBRCA1/2pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort ofBRCA1/2PV carriers ascertained through clinical genetic centres.

Methods

We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614BRCA1and 1365BRCA2PV 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 inBRCA1orBRCA2PV carriers. The full model identified 5.8%, 12.9% and 24.0% ofBRCA1/2PV 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 forBRCA1andBRCA2PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).

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