| 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; GEMO Study Collaborators; EMBRACE Collaborators; 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; Gayther, SA; Gerdes, A-M; Godwin, AK; Goldgar, DE; Hahnen, E; Hake, CR; Hamann, U; Hogervorst, FBL; Hooning, MJ; Hopper, JL; Hulick, PJ; Imyanitov, EN; OCGN Investigators; HEBON Investigators; KconFab Investigators; Isaacs, C; Izatt, L; Jakubowska, A; James, PA; Janavicius, R; Jensen, UB; Jiao, Y; John, EM; Joseph, V; Karlan, BY; Kets, CM; Konstantopoulou, I; Kwong, A; Legrand, C; Leslie, G; Lesueur, F; Loud, JT; Lubiński, J; Manoukian, S; McGuffog, L; Miller, A; Gomes, DM; Montagna, M; Mouret-Fourme, E; Nathanson, KL; Neuhausen, SL; Nevanlinna, H; Yie, JNY; Olah, E; Olopade, OI; Park, SK; Parsons, MT; Peterlongo, P; Piedmonte, M; Radice, P; Rantala, J; Rennert, G; Risch, HA; Schmutzler, RK; Sharma, P; Simard, J; Singer, CF; Stadler, Z; Stoppa-Lyonnet, D; Sutter, C; Tan, YY; Teixeira, MR; Teo, SH; Teulé, A; Thomassen, M; Thull, DL; Tischkowitz, M; Toland, AE; Tung, N; van Rensburg, EJ; Vega, A; Wappenschmidt, B; Devilee, P; van Asperen, CJ; Bernstein, JL; Offit, K; Easton, DF; Rookus, MA; Chenevix-Trench, G; Antoniou, AC; Robson, M; Schmidt, MK |
| Contributors: |
Eeles, Rosalind |
| Publisher Information: |
ELSEVIER SCIENCE INC |
| Publication Year: |
2021 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
GEMO Study Collaborators; EMBRACE Collaborators; OCGN Investigators; HEBON Investigators; KconFab Investigators |
| 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: |
Print-Electronic; application/pdf |
| Language: |
English |
| ISSN: |
1530-0366; 1098-3600 |
| Relation: |
Genetics in medicine : official journal of the American College of Medical Genetics, 2021; https://repository.icr.ac.uk/handle/internal/4753 |
| Availability: |
https://repository.icr.ac.uk/handle/internal/4753 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.264B03AF |
| Database: |
BASE |