Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers.
J Med Genet
; 61(8): 803-809, 2024 Jul 19.
Article
de En
| MEDLINE
| ID: mdl-38834293
ABSTRACT
BACKGROUND:
No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 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 BRCA1/2 PV carriers ascertained through clinical genetic centres.METHODS:
We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 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 BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 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 BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https//www.canrisk.org/).Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Protéine BRCA1
/
Prédisposition génétique à une maladie
/
Protéine BRCA2
/
Hétérozygote
Limites:
Adult
/
Female
/
Humans
/
Middle aged
Langue:
En
Journal:
J Med Genet
Année:
2024
Type de document:
Article
Pays d'affiliation:
Royaume-Uni