Validation of the BOADICEA Model in a Prospective Cohort of BRCA1/2 Pathogenic Variant Carriers (2024)

Competing Interest Statement

ACA and DFE are named creators of the BOADICEA model which has been licensed by Cambridge Enterprise (University of Cambridge). All the other authors declare no conflict of interest.

Funding Statement

This work was supported by TRANsIBCCS JT (2021/cancer12-054); NKI2013-6403 and by grants from Cancer Research UK (C12292/A20861 and PPRPGM-Nov20\100002) and by the NIHR Cambridge BRC. The national French cohort, GENEPSO, was initially funded by grants from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by Institut National du Cancer-DGOS, grant PRT-K22-076 and by the Programmes labellisés (PGA) 2022 of the Fondation ARC (NARCPGA2022010004414_4863). It also received support from the European commission FP6 (Project GEN-RAD-RISK 2005) and the French National Institute of Cancer (INCa SHS-E-SP 2008, 2011, 2015; CANSOP 2014). GENEPSO is supported for this project by an INCa grant as part of the European program ERA-NET on Translational Cancer Research (TRANsIBCCS-JTC2012, no. 2014-008). The GEMO biobank was initially funded by the French National Institute of Cancer (INCa, PHRC Ile de France, grant AOR 01 082, 2001-2003, grant 2013-1-BCB-01-ICH-1), the Association Le cancer du sein, parlons-en Award (2004), the Association for International Cancer Research (2008-2010), and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). It also received support from the Canadian Institute of Health Research for the CIHR Team in Familial Risks of Breast Cancer program (2008-2013), and the European commission FP7, Project Collaborative Ovarian, breast and prostate Gene-environment Study (COGS), Large-scale integrating project (2009-2013). GEMO is currently supported by the INCa grant SHS-E-SP 18-015. MT was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The International Hereditary Cancer Centre (IHCC) was supported by Grant PBZ_KBN_122/P05/2004 and The National Centre for Research and Development (NCBR) within the framework of the international ERA-NET TRANSAN JTC 2012 application no. Cancer 12-054 (Contract No. ERA-NET-TRANSCAN/07/2014). The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, NKI 12535, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12-054.MT was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).We acknowledge the GENEPSO Coordinating Center: DRCI, Institut Paoli-Calmettes, Marseille, France: Catherine Noguès, MD, Lilian Laborde, Emanuelle Breysse, Anne Robert-Bourgoin, Ulysse Bousquet, Pauline Heux; the genetic epidemiology platform (the PIGE, Plateforme dInvestigation en Génétique et Epidémiologie, Institut Curie, Paris) and particularly Juana Beauvallet who centralised, digitalized mammograms and coded and computed pedigrees data for the TRANsIBCCS Project. We acknowledge the GENEPSO Collaborating Centres and Investigators. We also acknowledge investigators of the Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carrier (GEMO) study from the National Cancer Genetics Network UNICANCER Genetic Group, France. GEMO contributed in providing genotype data of the GENEPSO participants thanks to its participation to CIMBA consortium. We thank Noura Mebirouk who managed the GEMO samples, Sandrine Caputo who maintains the French BRCA1/2 variants database and helped verifying variants nomenclature and classification, and Yue Jiao who developed the record linkage process to make GEMO and GENEPSO databases interoperable.The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, Netherlands (NL); Erasmus Medical Center, Rotterdam, NL; Leiden University Medical Center, NL; Radboud University Medical Center Nijmegen, NL; University Medical Center Utrecht, NL; Amsterdam UMC, University of Amsterdam, NL; Amsterdam UMC, Vrije Universiteit Amsterdam, NL; Maastricht University Medical Center, NL; University of Groningen, NL; The Netherlands Comprehensive Cancer Organisation (IKNL; The nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA). HEBON thanks all study participants. GC-HBOC is supported for this project by a BMBF grant (01KT1405) as part of the European program ERA-NET on Translational Cancer Research (TRANsIBCCS-JTC2012, no. 2014-008). The GC-HBOC is supported by the German Cancer Aid (grant no 110837 and grant no 70114178, coordinator: Rita K. Schmutzler, Cologne) and the Federal Ministry of Education and Research (BMBF), Germany (grant no 01GY1901).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by local ethics committees and all individuals gave informed consent. TRANsIBCCS consists six study centres including GC-HBOC, EMBRACE, GENEPSO, HEBON, MUV and IHCC. GC-HBOC was approved by the Ethics Commission of Cologne University’s Faculty of Medicine (07/048), the Ethics Commission of Dresden University’s Faculty of Medicine (EK 205052015), the Ethics Commission of the Technical University Munich, Rechts der Isar, Faculty of Medicine (169/15s), the Ethics Commission of Düsseldorf University’s Faculty of Medicine (4884), the Ethics Commission of Kiel University’s Faculty of Medicine, the Ethic Commission of Hannover Medical School (Nr. 4121), the Ethics Commission of Münster University’s Faculty of Medicine. EMBRACE was approved by the East of England - Cambridge South Research Ethics Committee (MREC 98/5/27). GENEPSO was approved by the Commission Nationale de l’Informatique et des Libertés (CNIL agreement N999350V4-2017). The genetic data for GENEPSO participants are collected via the partner GEMO study. GEMO was reviewed by the Comité consultatif sur le traitement de I’information en matière de recherche dans le domaine de la santé (CCTIRS N07223) and Commission Nationale de l’Informatique et des Libertés (CNIL N1245228) and was considered compliant with the General Data Protection Regulation and was approved by the institutional review committee of Institut Curie on April 2020. HEBON was approved by the Protocol Toetsingscommissie van het Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis (PTC07.1611/2007NKI-2007-375). MUV was approved by the Ethikkommission der Medizinischen Universität Wien (2190/2019). IHCC was approved by the Komisja Bioetyczna Pomorskiego Uniwersytetu Medycznego w Szczecinie (Bioethics Committee of Pomeranian Medical University in Szczecin; BN-001/33/04).

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Yes

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Yes

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Yes