TY - JOUR
T1 - 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
AU - OCGN Investigators
AU - Lakeman, Inge M. M.
AU - van den Broek, Alexandra J.
AU - Vos, Juliën A. M.
AU - Barnes, Daniel R.
AU - Adlard, Julian
AU - Andrulis, Irene L.
AU - Arason, Adalgeir
AU - Arnold, Norbert
AU - Arun, Banu K.
AU - Balmaña, Judith
AU - Barrowdale, Daniel
AU - Benitez, Javier
AU - Borg, Ake
AU - Caldés, Trinidad
AU - Caligo, Maria A.
AU - Chung, Wendy K.
AU - Claes, Kathleen B. M.
AU - Barouk-Simonet, Emmanuelle
AU - Belotti, Muriel
AU - Berthet, Pascaline
AU - Bignon, Yves-Jean
AU - Bonadona, Valérie
AU - Bressac-de Paillerets, Brigitte
AU - Buecher, Bruno
AU - Caputo, Sandrine
AU - Caron, Olivier
AU - Castera, Laurent
AU - Caux-Moncoutier, Virginie
AU - Colas, Chrystelle
AU - Collonge-Rame, Marie-Agnès
AU - Coupier, Isabelle
AU - de Pauw, Antoine
AU - Delnatte, Capucine
AU - Elan, Camille
AU - Faivre, Laurence
AU - Ferrer, Sandra Fert
AU - Gauthier-Villars, Marion
AU - Gesta, Paul
AU - Giraud, Sophie
AU - Golmard, Lisa
AU - Houdayer, Claude
AU - Lasset, Christine
AU - Laurent, Maïté
AU - Leroux, Dominique
AU - Longy, Michel
AU - Mari, V. ronique
AU - Aalfs, Cora M.
AU - HEBON Investigators
AU - KConFab Investigators
AU - Meijers-Heijboer, Hanne E. J.
AU - GEMO Study Collaborators
AU - van Engelen, Klaartje
AU - EMBRACE Collaborators
AU - van Os, Theo A. M.
AU - Collée, J. Margriet
AU - Hooning, Maartje J.
AU - Adank, Muriel A.
AU - Blok, Marinus J.
AU - Oosterwijk, Jan C.
AU - van Hest, Liselotte P.
N1 - Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS 313) 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 PRS 313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS 313 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 PRS 313, 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 PRS 313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS 313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS 313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
AB - Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS 313) 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 PRS 313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS 313 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 PRS 313, 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 PRS 313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS 313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS 313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
UR - http://www.scopus.com/inward/record.url?scp=85115935642&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41436-021-01198-7
DO - https://doi.org/10.1038/s41436-021-01198-7
M3 - Article
C2 - 34113011
SN - 1098-3600
VL - 23
SP - 1726
EP - 1737
JO - Genetics in medicine
JF - Genetics in medicine
IS - 9
ER -