| 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, IMM; van den Broek, AJ; Vos, JAM; Barnes, DR; Adlard, J; Andrulis, IL; Arason, A; Arnold, N; Arun, BK; Balmaña, J; Barrowdale, D; Benitez, J; Borg, A; Caldés, T; Caligo, MA; Chung, WK; Claes, KBM; Barouk-Simonet, E; Belotti, M; Berthet, P; Bignon, YJ; Bonadona, V; Bressac-de Paillerets, B; Buecher, B; Caputo, S; Caron, O; Castera, L; Caux-Moncoutier, V; Colas, C; Collonge-Rame, MA; Coupier, I; de Pauw, A; Delnatte, C; Elan, C; Faivre, L; Ferrer, SF; Gauthier-Villars, M; Gesta, P; Giraud, S; Golmard, L; Houdayer, C; Lasset, C; Laurent, M; Leroux, D; Longy, M; Mari, V; Mazoyer, S; Mebirouk, N; Mortemousque, I; Prieur, F; Pujol, P; Saule, C; Schuster, H; Sevenet, N; Sobol, H; Sokolowska, J; Venat-Bouvet, L; Ahmed, M; Barwell, J; Brady, A; Brennan, P; Brewer, C; Cook, J; Davidson, R; Donaldson, A; Dunning, AM; Eason, J; Eccles, DM; Gregory, H; Hanson, H; Harrington, PA; Henderson, A; Hodgson, S; Kennedy, MJ; Lalloo, F; Miller, C; Morrison, PJ; Ong, KR; O’Shaughnessy-Kirwan, A; Perkins, J; Porteous, ME; Rogers, MT; Side, LE; Snape, K; Walker, L; Collée, JM; Couch, FJ; Daly, MB; Dennis, J; Dhawan, M; Domchek, SM; Eeles, R; Engel, C; Evans, DG; Feliubadaló, L; Foretova, L; Friedman, E; Frost, D; Ganz, PA; Garber, J |
| Publisher Information: |
ELSEVIER SCIENCE INC |
| Publication Year: |
2021 |
| Collection: |
The University of Melbourne: Digital Repository |
| 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 |
| Language: |
English |
| ISSN: |
1098-3600 |
| Relation: |
https://hdl.handle.net/11343/281009 |
| Availability: |
https://hdl.handle.net/11343/281009 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.9F709349 |
| Database: |
BASE |