| Title: |
Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers. |
| Authors: |
Yang, Xin; Mooij, Thea M; Leslie, Goska; Ficorella, Lorenzo; Andrieu, Nadine; Kast, Karin; Singer, Christian F; Jakubowska, Anna; van Gils, Carla H; Tan, Yen Y; Engel, Christoph; Adank, Muriel A; van Asperen, Christi J; Ausems, Margreet GEM; Berthet, Pascaline; EMBRACE collaborators; Collee, Margriet J; Cook, Jackie A; Eason, Jacqueline; Spaendonck-Zwarts, Karin Y van; Evans, D Gareth; Gómez García, Encarna B; Hanson, Helen; Izatt, Louise; Kemp, Zoe; Lalloo, Fiona; Lasset, Christine; Lesueur, Fabienne; Musgrave, Hannah; Nambot, Sophie; Noguès, Catherine; Oosterwijk, Jan C; Stoppa-Lyonnet, Dominique; Tischkowitz, Marc; Tripathi, Vishakha; Wevers, Marijke R; Zhao, Emily; van Leeuwen, Flora E; Schmidt, Marjanka K; Easton, Douglas F; Rookus, Matti A; Antoniou, Antonis C |
| Publisher Information: |
BMJ; //doi.org/10.1136/jmg-2024-109943 |
| Publication Year: |
2024 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Early Diagnosis; Genetic Counseling; Public Health; Women's Health; Humans; Female; Breast Neoplasms; BRCA2 Protein; BRCA1 Protein; Middle Aged; Adult; Prospective Studies; Heterozygote; Genetic Predisposition to Disease; Risk Factors; Risk Assessment; Polymorphism; Single Nucleotide |
| Description: |
Peer reviewed: True ; Funder: NIHR Cambridge BRC ; 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 |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; text/xml |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/369494 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/369494 |
| Rights: |
Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.F8D7D4CF |
| Database: |
BASE |