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 - GEMO Study Collaborators
AU - EMBRACE Collaborators
AU - OCGN Investigators
AU - HEBON Investigators
AU - KConFab 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, Véronique
AU - Mazoyer, Sylvie
AU - Mebirouk, Noura
AU - Mortemousque, Isabelle
AU - Daly, Mary B.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85115935642
U2 - 10.1038/s41436-021-01198-7
DO - 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 -
SDG 3 Good Health and Well-being