| Title: |
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 |
| Authors: |
Lakeman, Inge MM; van den Broek, Alexandra J; Vos, Juliën AM; Barnes, Daniel R; Adlard, Julian; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Balmaña, Judith; Barrowdale, Daniel; Benitez, Javier; Borg, Ake; Caldés, Trinidad; Caligo, Maria A; Chung, Wendy K; Claes, Kathleen BM; Collaborators, GEMO Study; Barouk-Simonet, Emmanuelle; Belotti, Muriel; Berthet, Pascaline; Bignon, Yves-Jean; Bonadona, Valérie; Paillerets, Brigitte Bressac-de; Buecher, Bruno; Caputo, Sandrine; Caron, Olivier; Castera, Laurent; Caux-Moncoutier, Virginie; Colas, Chrystelle; Collonge-Rame, Marie-Agnès; Coupier, Isabelle; de Pauw, Antoine; Delnatte, Capucine; Elan, Camille; Faivre, Laurence; Ferrer, Sandra Fert; Gauthier-Villars, Marion; Gesta, Paul; Giraud, Sophie; Golmard, Lisa; Houdayer, Claude; Lasset, Christine; Laurent, Maïté; Leroux, Dominique; Longy, Michel; Mari, Véronique; Mazoyer, Sylvie; Mebirouk, Noura; Mortemousque, Isabelle; Prieur, Fabienne; Pujol, Pascal; Saule, Claire; Schuster, Helene; Sevenet, Nicolas; Sobol, Hagay; Sokolowska, Johanna; Venat-Bouvet, Laurence; Collaborators, EMBRACE; Ahmed, Munaza; Barwell, Julian; Brady, Angela; Brennan, Paul; Brewer, Carole; Cook, Jackie; Davidson, Rosemarie; Donaldson, Alan; Dunning, Alison M; Eason, Jacqueline; Eccles, Diana M; Gregory, Helen; Hanson, Helen; Harrington, Patricia A; Henderson, Alex; Hodgson, Shirley; Kennedy, M John; Lalloo, Fiona; Miller, Clare; Morrison, Patrick J; Ong, Kai-ren; O’Shaughnessy-Kirwan, Aoife; Perkins, Jo; Porteous, Mary E; Rogers, Mark T; Side, Lucy E; Snape, Katie; Walker, Lisa; Collée, J Margriet; Couch, Fergus J; Daly, Mary B; Dennis, Joe; Dhawan, Mallika; Domchek, Susan M; Eeles, Ros; Engel, Christoph; Evans, D Gareth; Feliubadaló, Lidia; Foretova, Lenka; Friedman, Eitan; Frost, Debra |
| Source: |
Genetics in Medicine, vol 23, iss 9 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
31 Biological Sciences (for-2020); 3105 Genetics (for-2020); Prevention (rcdc); Women's Health (rcdc); Breast Cancer (rcdc); Cancer (rcdc); Genetics (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Cancer (hrcs-hc); Adult (mesh); BRCA1 Protein (mesh); BRCA2 Protein (mesh); Breast Neoplasms (mesh); Female (mesh); Genetic Predisposition to Disease (mesh); Heterozygote (mesh); Humans (mesh); Mutation (mesh); Retrospective Studies (mesh); Risk Factors (mesh); GEMO Study Collaborators; EMBRACE Collaborators; OCGN Investigators; HEBON Investigators; KconFab Investigators; 0604 Genetics (for); 1103 Clinical Sciences (for); Genetics & Heredity (science-metrix) |
| Time: |
1726 - 1737 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt9c71h04q; https://escholarship.org/uc/item/9c71h04q; https://escholarship.org/content/qt9c71h04q/qt9c71h04q.pdf |
| DOI: |
10.1038/s41436-021-01198-7 |
| Availability: |
https://escholarship.org/uc/item/9c71h04q; https://escholarship.org/content/qt9c71h04q/qt9c71h04q.pdf; https://doi.org/10.1038/s41436-021-01198-7 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.C1C556CF |
| Database: |
BASE |