← Back to cohort
The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
Inge M. M. Lakeman, Alexandra J. van den Broek, Julien A M Vos, Daniel R. Barnes, Julian Adlard, Irene L. Andrulis, Aðalgeir Arason, Norbert Arnold, Banu Arun, Judith Balmañà, Daniel Barrowdale, Javier Benı́tez, Åke Borg, Trinidad Caldés, Maria A. Caligo, Wendy K. Chung, Kathleen Claes, Emmanuelle Barouk-Simonet, Muriel Belotti, Pascaline Berthet, Yves‐Jean Bignon, Valérie Bonadona, Brigitte Bressac–de Paillerets, Bruno Buecher, Sandrine M. Caputo, Olivier Caron, Laurent Castera, Virginie Caux‐Moncoutier, Chrystelle Colas, Marie‐Agnès Collonge‐Rame, Isabelle Coupier, Antoine De Pauw, Capucine Delnatte, Camille Elan, Laurence Faivre, Sandra Fert Ferrer, Marion Gauthier-Villars, Paul Gesta, Sophie Giraud, Lisa Golmard, Claude Houdayer, Christine Lasset, Dominique Leroux, Michel Longy, Véronique Mari, Sylvie Mazoyer, Noura Mebirouk, Isabelle Mortemousque, Fabienne Prieur, Pascal Pujol, Claire Saule, Helene Schuster, Nicolas Sévenet, Hagay Sobol, Johanna Sokolowska, Laurence Venat‐Bouvet, Munaza Ahmed, Julian Barwell, Angela Brady, Paul Brennan, Carole Brewer, Jackie Cook, Rosemarie Davidson, Alan Donaldson, Alison M. Dunning, Jacqueline Eason, Helen Gregory, Helen Hanson, Patricia A. Harrington, Alex Henderson, Shirley Hodgson, Michael J. Kennedy, Fiona Lalloo, Clare Miller, Patrick J. Morrison, Kai‐Ren Ong, Aoife O’Shaughnessy-Kirwan, Jo Perkins, Mary Porteous, Mark T. Rogers, Lucy Side, Katie Snape, Lisa Walker, J. Margriet Collée, Fergus J. Couch, Mary B. Daly, Joe Dennis, Mallika Dhawan, Susan M. Domchek, Ros Eeles, Christoph Engel, D. Gareth Evans, Lídia Feliubadaló, Lenka Foretová, Eitan Friedman, Debra Frost, Patricia A. Ganz, Judy Garber, Simon A. Gayther, Anne‐Marie Gerdes, Andrew K. Godwin, David E. Goldgar, Eric Hahnen, Christopher R. Hake, U. Hamann, Frans B.L. Hogervorst, Maartje J. Hooning, John L. Hopper, Peter J. Hulick, Evgeny N. Imyanitov, Gord Glendon, Anna Marie Mulligan, Christi J. van Asperen, Cora M. Aalfs, Muriel A. Adank, Margreet G.E.M. Ausems, Marinus J. Blok, Encarna B. Gómez Garcia, Bernadette A. M. Heemskerk‐Gerritsen, Antoinette Hollestelle, Agnes Jager, Linetta B. Koppert, Marco J. Koudijs, Mieke Kriege, Hanne Meijers‐Heijboer, Arjen R. Mensenkamp, Thea M. Mooij, Jan C. Oosterwijk, Ans M.W. van den Ouweland, Frederieke H. van der Baan, Annemieke H. van der Hout, Lizet E. van der Kolk, Rob B. van der Luijt, Carolien H. M. van Deurzen, Helena C. van Doorn, Klaartje van Engelen, Liselotte P. van Hest, Theo A.M. van Os, Senno Verhoef, Maartje J. Vogel, Juul T. Wijnen, Jonathan Beesley, Stephen Fox, Helene Holland, Kelly‐Anne Phillips, Amanda B. Spurdle, Claudine Isaacs, Louise Izatt, Anna Jakubowska, Paul A. James, Ramūnas Janavičius, Uffe Birk Jensen, Yue Jiao, Esther M. John, Joseph Vijai, Beth Karlan, Carolien M. Kets, Irene Konstantopoulou, Ava Kwong, Clémentine Legrand, Goska Leslie, Jennifer T. Loud, Jan Lubiński, Siranoush Manoukian, Lesley McGuffog, Austin Miller, D. Molina Gomes, Marco Montagna, Emmanuelle Mouret‐Fourme, Katherine L. Nathanson, Susan L. Neuhausen, Heli Nevanlinna, Edith Olah, Olufunmilayo I. Olopade, Sue K. Park, Michael T. Parsons, Paolo Peterlongo, Marion Piedmonte, Paolo Radice, Johanna Rantala, Gad Rennert, Harvey A. Risch, Rita K. Schmutzler, Priyanka Sharma, Jacques Simard, Christian F. Singer, Zsofia Stadler, Dominique Stoppa‐Lyonnet, Christian Sutter, Yen Y. Tan, Manuel R. Teixeira, Soo‐Hwang Teo, Àlex Teulé, Mads Thomassen, Darcy L. Thull, Marc Tischkowitz, Amanda E. Toland, Nadine Tung, Elizabeth J. van Rensburg, Ana Vega, Barbara Wappenschmidt, Peter Devilee, Jonine L. Bernstein, Kenneth Offit, Douglas F. Easton, Matti A. Rookus, Georgia Chenevix‐Trench, Antonis C. Antoniou, Mark E. Robson, Marjanka K. Schmidt
Bibliographic record
VenueGenetics in Medicine · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsMcGill UniversityUniversité LavalUniversity of TorontoUniversity Health NetworkCentre hospitalier universitaire de QuébecLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersEuropean Social FundNational Center for Advancing Translational SciencesInstituto de Salud Carlos IIIMedical Research CouncilCanadian Institutes of Health ResearchCancer Center, University of KansasNational Institutes of HealthCentro de Investigación Biomédica en Red de CáncerFox Chase Cancer CenterMinistero dello Sviluppo EconomicoDeutsche KrebshilfeNational Health and Medical Research CouncilFisher Center for Alzheimer's Research FoundationJewish General HospitalRoyal Marsden NHS Foundation TrustCentres de Recerca de CatalunyaIstituto Oncologico VenetoDeutsches KrebsforschungszentrumClalit Health ServicesLietuvos Mokslo TarybaOvarian Cancer Research FundMinisterio de Economía y CompetitividadLandspítali HáskólasjúkrahúsKorea Health Industry Development InstituteHungarian Scientific Research FundNederlandse Organisatie voor Wetenschappelijk OnderzoekMinistero della SaluteKerry Group Kuok FoundationGeneralitat de CatalunyaNational Cancer InstituteLiga Portuguesa Contra o CancroRussian Foundation for Basic ResearchMinisterstvo Školství, Mládeže a TělovýchovyNational Breast Cancer FoundationWellcome TrustMemorial Sloan-Kettering Cancer CenterFondation du cancer du sein du QuébecNational Institute for Health and Care ResearchNemzeti Kutatási Fejlesztési és Innovációs HivatalGovernment of CanadaIsrael Cancer AssociationFundación Mutua MadrileñaMinistère du Développement Économique, de l’Innovation et de l’ExportationKWF KankerbestrijdingCancer Research UKAssociazione Italiana per la Ricerca sul CancroGenome CanadaBreast Cancer Research FoundationUniverzita Karlova v PrazeMcGill UniversityNational Institute of General Medical SciencesInstitut National Du CancerKansas Bioscience AuthorityCancer Association of South AfricaBeth Israel Deaconess Medical CenterGeorgetown UniversityFonds Wetenschappelijk OnderzoekEuropean Commission
KeywordsPolygenic risk scoreBreast cancerMedicineOncologyCancerInternal medicineGeneticsBiologySingle-nucleotide polymorphismGenotypeGene
Abstract
PURPOSE: ) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: and CBC risk. RESULTS: 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.330
Threshold uncertainty score0.486
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.012
GPT teacher head0.260
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations38
Published2021
Admission routes2
Has abstractyes