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Record W4400024420 · doi:10.17615/facv-0d26

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis

2024· article· en· W4400024420 on OpenAlexfundno aff
Jose E. Castelao, Julia Geisler, R.M. Tamimi, Maria Escala-Garcia, Sara Margolin, Minouk J. Schoemaker, Anna Jakubowska, Anthony J. Swerdlow, Alison M. Dunning, David J. Hunter, Melanie Gündert, Harald Surowy, Jaana M. Hartikainen, Peter Kraft, Niclas Håkansson, Thomas Rüdiger, Q. Wang, M.A. Troester, Diether Lambrechts, M. Daly, William Jacot, Kamila Czene, M.W. Beckmann, Heli Nevanlinna, Heiko Becher, Thilo Dörk, Annelie Augustinsson, Kyriaki Michailidou, Tjoung‐Won Park‐Simon, kConFab AOCS Investigators, Manjeet K. Bolla, Atocha Romero, Arif B. Ekici, Ian Tomlinson, D. Mavroudis, P.D.P. Pharoah, M Schmidt, Celine M. Vachon, Georgia Chenevix‐Trench, F.J. Couch, Joe Dennis, A.F. Olshan, J. Chang-Claude, R. Kaaks, Renske Keeman, Hedy S. Rennert, Sander Canisius, Antoinette Hollestelle, U. Hamann, Vessela N. Kristensen, Robert Winqvist, L. Le Marchand, Christopher J. Scott, Hermann Brenner, Lauren R. Teras, T. Bachelot, Per Hall, A. Wolk, Emilie Thomas, Sabine Behrens, Matthias Ruebner, Jan Lubiński, Linetta B. Koppert, T.A. Muranen, R.K. Schmutzler, K. Punie, Melissa C. Southey, Esther M. John, A. Heather Eliassen, Håkan Olsson, Э. К. Хуснутдинова, J. Beesley, Robert Luben, P. Peterlongo, Reiner Hoppe, Volker Arndt, P. Devilee, Elinor J. Sawyer, Masood Manoochehri, A. Lindblom, José Á. García-Sáenz, Argyrios Ziogas, S.J. Chanock, Paolo Radice, Stig E. Bojesen, Arto Mannermaa, D.F. Easton, H. Anton-Culver, Audrey Jung, Mervi Grip, P.A. Fasching, Federico Canzian, Montserrat García‐Closas, G. Rennert, Christopher A. Haiman, Rebecca Roylance, B.A.M. Heemskerk-Gerritsen, A.V. Patel, Graham G. Giles, Allison W. Kurian, Manuela Gago-Domínguez, Emmanouil Saloustros, John L. Hopper, Marina Bermisheva, Henrik Flyger

Bibliographic record

VenueUNC Libraries · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBRCA gene mutations in cancer
Canadian institutionsnot available
FundersNational Cancer InstituteServicio Gallego de SaludInstituto de Salud Carlos IIICancer Council VictoriaOulun YliopistoNational Health and Medical Research CouncilMedical Research CouncilCenters for Disease Control and PreventionHellenic Health FoundationXunta de GaliciaInstitut Gustave-RoussyNorges ForskningsrådDeutsche KrebshilfeInstitut National de la Santé et de la Recherche MédicaleUniversity of CreteVetenskapsrådetStockholms Läns LandstingWorld Cancer Research FundStavros Niarchos FoundationKuopion Yliopistollinen SairaalaKarolinska InstitutetGovernment of CanadaMinisterio de Sanidad, Servicios Sociales e IgualdadNational Institutes of HealthGentofte HospitalDeutsche Gesetzliche UnfallversicherungMutuelle Générale de l'Education NationaleOvarian Cancer Research FundBundesministerium für Bildung und ForschungMinisterio de Economía y CompetitividadCanadian Institutes of Health ResearchCancerfondenNational Institute for Health and Care ResearchEuropean Regional Development FundAcademy of FinlandKing's College LondonRobert Bosch StiftungKWF KankerbestrijdingCancer Research UKFreistaat SachsenAmerican Cancer SocietyKreftforeningenSundhed og Sygdom, Det Frie ForskningsrådCentre International de Recherche sur le CancerLigue Contre le CancerDeutsches KrebsforschungszentrumAssociazione Italiana per la Ricerca sul CancroGenome CanadaItä-Suomen YliopistoFondation du cancer du sein du QuébecEuropean CommissionBreast Cancer Research Foundation
KeywordsBreast cancerOncologyMedicineGermlineInternal medicineCancerBiologyGeneticsGene

Abstract

fetched live from OpenAlex

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10−8 and 4.42 × 10−8). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.

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 score0.017
Threshold uncertainty score0.674

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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 head0.009
GPT teacher head0.234
Teacher spread0.226 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

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