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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
IMM. Lakeman, AJ. van den Broek, JAM. Vos, DR. Barnes, J. Adlard, IL. Andrulis, A. Arason, N. Arnold, BK. Arun, J. Balmaña, D. Barrowdale, J. Benitez, A. Borg, T. Caldés, MA. Caligo, WK. Chung, KBM. Claes, GEMO Study Collaborators, EMBRACE...
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Grant support
UL1 TR000124
NCATS NIH HHS - United States
R01 CA214545
NCI NIH HHS - United States
C1287/A16563
Cancer Research UK - United Kingdom
P30 CA168524
NCI NIH HHS - United States
C5047/A10692
Cancer Research UK - United Kingdom
A11174
Cancer Research UK - United Kingdom
C5047/A8384
Cancer Research UK - United Kingdom
P30 CA008748
NCI NIH HHS - United States
U19 CA148065
NCI NIH HHS - United States
P20 GM130423
NIGMS NIH HHS - United States
RC4 CA153828
NCI NIH HHS - United States
C1281/A12014
Cancer Research UK - United Kingdom
C12292/A2086
Cancer Research UK - United Kingdom
C12292/A11174
Cancer Research UK - United Kingdom
Department of Health - United Kingdom
C1287/A 10710
Cancer Research UK - United Kingdom
CIHR - Canada
U10 CA180822
NCI NIH HHS - United States
C5047/A15007
Cancer Research UK - United Kingdom
UM1 CA164920
NCI NIH HHS - United States
U10 CA180868
NCI NIH HHS - United States
UL1 TR001881
NCATS NIH HHS - United States
C8197/A16565
Cancer Research UK - United Kingdom
C1287/A10118
Cancer Research UK - United Kingdom
R25 CA112486
NCI NIH HHS - United States
NLK
ProQuest Central
from 2011-01-01 to 2021-12-31
Health & Medicine (ProQuest)
from 2011-01-01 to 2021-12-31
ROAD: Directory of Open Access Scholarly Resources
from 1998
- MeSH
- Adult MeSH
- Genetic Predisposition to Disease MeSH
- Heterozygote MeSH
- Humans MeSH
- Mutation MeSH
- Breast Neoplasms * diagnosis epidemiology genetics MeSH
- BRCA1 Protein genetics MeSH
- BRCA2 Protein genetics MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
Basser Center for BRCA Abramson Cancer Center University of Pennsylvania Philadelphia PA USA
Biomedical Sciences Institute University of Porto Porto Portugal
BMC Faculty of Medicine University of Iceland Reykjavik Iceland
Breast Cancer Research Programme Cancer Research Malaysia Subang Jaya Selangor Malaysia
Cancer Genetics and Prevention Program University of California San Francisco San Francisco CA USA
Cancer Genetics Service National Cancer Centre Singapore Singapore
Cancer Research Institute Seoul National University Seoul Korea
Cancer Risk and Prevention Clinic Dana Farber Cancer Institute Boston MA USA
Center for Clinical Cancer Genetics The University of Chicago Chicago IL USA
Center for Medical Genetics NorthShore University HealthSystem Evanston IL USA
Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge UK
Centre for Medical Genetics Ghent University Ghent Belgium
Centro de Investigación en Red de Enfermedades Raras Madrid Spain
Chronic Disease Epidemiology Yale School of Public Health New Haven CT USA
Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London UK
Clinical Genetics Karolinska Institutet Stockholm Sweden
Département de Génétique CHU de Grenoble Grenoble France
Department of Biomedical Sciences Seoul National University Graduate School Seoul Korea
Department of Breast Medical Oncology University of Texas MD Anderson Cancer Center Houston TX USA
Department of Cancer Biology and Genetics The Ohio State University Columbus OH USA
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark
Department of Clinical Genetics Erasmus University Medical Center CA Rotterdam The Netherlands
Department of Clinical Genetics Fox Chase Cancer Center Philadelphia PA USA
Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands
Department of Clinical Genetics Odense University Hospital Odence C Denmark
Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark
Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA
Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland
Department of Genetics Portuguese Oncology Institute Porto Portugal
Department of Genetics University of Pretoria Arcadia South Africa
Department of Human Genetics Leiden University Medical Center Leiden The Netherlands
Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN USA
Department of Medical Oncology Beth Israel Deaconess Medical Center Boston MA USA
Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Department of Molecular Genetics University of Toronto Toronto ON Canada
Department of Oncology Lund University and Skåne University Hospital Lund Sweden
Department of Pathology Landspitali University Hospital Reykjavik Iceland
Department of Pathology Leiden University Medical Center Leiden The Netherlands
Department of Population Sciences Beckman Research Institute of City of Hope Duarte CA USA
Department of Preventive Medicine Seoul National University College of Medicine Seoul Korea
Department of Surgery Faculty of Medicine University of Malaya Kuala Lumpur Malaysia
Department of Surgery Hong Kong Sanatorium and Hospital Happy Valley Hong Kong
Department of Surgery The University of Hong Kong Pok Fu Lam Hong Kong
Department of Tumour Biology INSERM U830 Paris France
Departments of Pediatrics and Medicine Columbia University New York NY USA
Dept of OB GYN and Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Dept of OB GYN Medical University of Vienna Vienna Austria
Fundación Pública Galega de Medicina Xenómica Santiago de Compostela Spain
Genetic Epidemiology of Cancer team Paris France
Genome Diagnostics Program IFOM the FIRC Institute of Molecular Oncology Milan Italy
Hereditary cancer Genetics Group Vall d'Hebron Institute of Oncology Barcelona Spain
Hong Kong Hereditary Breast Cancer Family Registry Cancer Genetics Centre Happy Valley Hong Kong
Human Cancer Genetics Programme Spanish National Cancer Research Centre Madrid Spain
Immunology and Molecular Oncology Unit Veneto Institute of Oncology IOV IRCCS Padua Italy
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany
Institute of Human Genetics University Hospital Heidelberg Heidelberg Germany
Lee Kong Chian School of Medicine Nanyang Technological University Singapore Singapore
Lombardi Comprehensive Cancer Center Georgetown University Washington DC USA
Mines ParisTech Fontainebleau France
Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany
Molecular Oncology Laboratory CIBERONC Hospital Clinico San Carlos IdISSC Madrid Spain
N N Petrov Institute of Oncology St Petersburg Russia
NRG Oncology Statistics and Data Management Center Roswell Park Cancer Institute Buffalo NY USA
Oncogenetics Team The Institute of Cancer Research and Royal Marsden NHS Foundation Trust London UK
Parkville Familial Cancer Centre Peter MacCallum Cancer Center Melbourne VIC Australia
Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel
Service de Génétique Institut Curie Paris France
Sir Peter MacCallum Department of Oncology The University of Melbourne Melbourne VIC Australia
SOD Genetica Molecolare University Hospital Pisa Italy
State Research Institute Centre for Innovative Medicine Vilnius Lithuania
The Susanne Levy Gertner Oncogenetics Unit Chaim Sheba Medical Center Ramat Gan Israel
The University of Chicago Pritzker School of Medicine Chicago IL USA
Université Paris Descartes Paris France
Waukesha Memorial Hospital Pro Health Care Waukesha WI USA
Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds UK
References provided by Crossref.org
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- $a 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 / $c IMM. Lakeman, AJ. van den Broek, JAM. Vos, DR. Barnes, J. Adlard, IL. Andrulis, A. Arason, N. Arnold, BK. Arun, J. Balmaña, D. Barrowdale, J. Benitez, A. Borg, T. Caldés, MA. Caligo, WK. Chung, KBM. Claes, GEMO Study Collaborators, EMBRACE Collaborators, JM. Collée, FJ. Couch, MB. Daly, J. Dennis, M. Dhawan, SM. Domchek, R. Eeles, C. Engel, DG. Evans, L. Feliubadaló, L. Foretova, E. Friedman, D. Frost, PA. Ganz, J. Garber, SA. Gayther, AM. Gerdes, AK. Godwin, DE. Goldgar, E. Hahnen, CR. Hake, U. Hamann, FBL. Hogervorst, MJ. Hooning, JL. Hopper, PJ. Hulick, EN. Imyanitov, OCGN Investigators, HEBON Investigators, KconFab Investigators, C. Isaacs, L. Izatt, A. Jakubowska, PA. James, R. Janavicius, UB. Jensen, Y. Jiao, EM. John, V. Joseph, BY. Karlan, CM. Kets, I. Konstantopoulou, A. Kwong, C. Legrand, G. Leslie, F. Lesueur, JT. Loud, J. Lubiński, S. Manoukian, L. McGuffog, A. Miller, DM. Gomes, M. Montagna, E. Mouret-Fourme, KL. Nathanson, SL. Neuhausen, H. Nevanlinna, JNY. Yie, E. Olah, OI. Olopade, SK. Park, MT. Parsons, P. Peterlongo, M. Piedmonte, P. Radice, J. Rantala, G. Rennert, HA. Risch, RK. Schmutzler, P. Sharma, J. Simard, CF. Singer, Z. Stadler, D. Stoppa-Lyonnet, C. Sutter, YY. Tan, MR. Teixeira, SH. Teo, A. Teulé, M. Thomassen, DL. Thull, M. Tischkowitz, AE. Toland, N. Tung, EJ. van Rensburg, A. Vega, B. Wappenschmidt, P. Devilee, CJ. van Asperen, JL. Bernstein, K. Offit, DF. Easton, MA. Rookus, G. Chenevix-Trench, AC. Antoniou, M. Robson, MK. Schmidt
- 520 9_
- $a PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
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