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Record W4383058646 · doi:10.1002/cam4.6272

Association of the <scp> <i>CHEK2</i> </scp> c. <scp>1100delC</scp> variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival

2023· article· en· W4383058646 on OpenAlexafffund
Anna Morra, Maartje A. C. Schreurs, Irene L. Andrulis, Hoda Anton‐Culver, Annelie Augustinsson, Matthias W. Beckmann, Sabine Behrens, Manjeet K. Bolla, Hiltrud Brauch, Annegien Broeks, Saundra S. Buys, Nicola J. Camp, Jose E. Castelao, Melissa H. Cessna, Jenny Chang‐Claude, Wendy K. Chung, Sarah V. Colonna, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Peter Devilee, Thilo Dörk, Alison M. Dunning, Miriam Dwek, Douglas F. Easton, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Tanja Fehm, Jonine D. Figueroa, Henrik Flyger, Marike Gabrielson, Manuela Gago-Domínguez, Montserrat García‐Closas, José Á. García-Sáenz, Jeanine M. Genkinger, Felix Graßmann, Melanie Gündert, Eric Hahnen, Christopher A. Haiman, Ute Hamann, Patricia Harrington, Jaana M. Hartikainen, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anna Jakubowska, Wolfgang Janni, Helena Jernström, Esther M. John, Nichola Johnson, Michael E. Jones, Vessela N. Kristensen, Allison W. Kurian, Diether Lambrechts, Loı̈c Le Marchand, Annika Lindblom, Jan Lubiński, Michael P. Lux, Dimitrios Mavroudis, Anna Marie Mulligan, Taru Muranen, Heli Nevanlinna, Ines Nevelsteen, Patrick Neven, William G. Newman, Nadia Obi, Kenneth Offit, Andrew F. Olshan, Tjoung‐Won Park‐Simon, Alpa V. Patel, Paolo Peterlongo, Kelly‐Anne Phillips, Dijana Plaseska‐Karanfilska, Eric C. Polley, Nadège Presneau, Katri Pylkäs, Brigitte Rack, Paolo Radice, Muhammad Usman Rashid, Valerie Rhenius, Mark E. Robson, Atocha Romero, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Sabine Schuetze, Christopher G. Scott, Mitul Shah, Snezhana Smichkoska, Melissa C. Southey, William Tapper, Lauren R. Teras, Rob A.�E.�M. Tollenaar, Katarzyna Tomczyk, Ian Tomlinson, Melissa A. Troester, Celine M. Vachon, Elke M. van Veen, Qin Wang, Camilla Wendt, Hans Wildiers, Robert Winqvist, Argyrios Ziogas, Per Hall, Paul D.P. Pharoah, Muriel A. Adank, Antoinette Hollestelle, Marjanka K. Schmidt, Maartje J. Hooning

Bibliographic record

VenueCancer Medicine · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsUniversity Health NetworkLunenfeld-Tanenbaum Research InstituteUniversity of TorontoMount Sinai Hospital
FundersMedical Research and Materiel CommandServicio Gallego de SaludUniversitätsklinikum Hamburg-EppendorfInstituto de Salud Carlos IIICancer Council TasmaniaWorld Cancer Research FundMedical Research CouncilCanadian Institutes of Health ResearchProgramme Grants for Applied ResearchManchester Biomedical Research CentreImperial Experimental Cancer Medicine CentreNational Institutes of HealthHellenic Health FoundationXunta de GaliciaRheinische Friedrich-Wilhelms-Universität BonnMutuelle Générale de l'Education NationaleInstitut Gustave-RoussyAgence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du TravailNational Health and Medical Research CouncilOulun YliopistoNational Center for Chronic Disease Prevention and Health PromotionDeutsche KrebshilfeCenters for Disease Control and PreventionInstitut National Du CancerLeids Universitair Medisch CentrumAssociazione Italiana per la Ricerca sul CancroKWF KankerbestrijdingSyöpäsäätiöVetenskapsrådetStockholms Läns LandstingLigue Contre le CancerKuopion Yliopistollinen SairaalaBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadEuropean Regional Development FundKing's College LondonAcademy of FinlandUniversity of CreteInstitut National de la Santé et de la Recherche MédicaleCancer AustraliaAgence Nationale de la RechercheHuntsman Cancer FoundationRobert Bosch StiftungFP7 Ideas: European Research CouncilAgency for Science, Technology and ResearchNational Institute of Environmental Health SciencesU.S. ArmyUniversity of WestminsterNational Breast Cancer FoundationEuropean CommissionCancer Council South AustraliaAmerican Cancer SocietyFonds Wetenschappelijk OnderzoekCancerfondenNational Cancer InstituteCancer Institute NSWFondation de FranceNIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer ResearchUniversity of UtahBreast Cancer CampaignSundhed og Sygdom, Det Frie ForskningsrådCentre International de Recherche sur le CancerDeutsches KrebsforschungszentrumDeutsche Gesetzliche UnfallversicherungGentofte HospitalNational Institute for Health and Care ResearchNorges ForskningsrådDivision of Cancer Prevention, National Cancer InstituteKarolinska InstitutetHarvard T.H. Chan School of Public HealthFreistaat SachsenHuntsman Cancer InstituteUniversity of CaliforniaIntermountain HealthcareCancer Council VictoriaCalifornia Department of Public HealthLon V. Smith FoundationGenome CanadaItä-Suomen YliopistoBrigham and Women's HospitalMinisterio de Sanidad, Servicios Sociales e IgualdadGovernment of CanadaUniversity of CambridgeBreast Cancer Research FoundationCancer Council NSWSusan G. Komen for the CureEberhard Karls Universität TübingenWellcome TrustFondation du cancer du sein du QuébecMemorial Sloan-Kettering Cancer CenterCancer Research UKStavros Niarchos FoundationUniversity of Southern CaliforniaKreftforeningenUniversity of California, San FranciscoU.S. Department of Health and Human Services
KeywordsBreast cancerMedicineOncologyInternal medicineRadiation therapySystemic therapyCancer

Abstract

fetched live from OpenAlex

BACKGROUND: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. METHODS: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. RESULTS: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. CONCLUSION: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

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 imitation

Not 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)0.000
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 score0.127
Threshold uncertainty score0.926

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.008
GPT teacher head0.248
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine 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

Citations10
Published2023
Admission routes2
Has abstractyes

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