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

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Lakeman, IMM (Author) Other; van den Broek, AJ (Author) Other; Vos, JAM (Author) Other; Barnes, DR (Author) Other; Adlard, J (Author) Other; Andrulis, IL (Author) Other; Arason, A (Author) Other; Arnold, N (Author) Other; Arun, BK (Author) Other; Balmana, J (Author) Other; Barrowdale, D (Author) Other; Benitez, J (Author) Other; Borg, A (Author) Other; Caldes, T (Author) Other; Caligo, MA (Author) Other; Chung, WK (Author) Other; Claes, KBM (Author) Other; Collee, JM (Author) Other; Couch, FJ (Author) Other; Daly, MB (Author) Other; Dennis, J (Author) Other; Dhawan, M (Author) Other; Domchek, SM (Author) Other; Eeles, R (Author) Other; Engel, C (Author) Other; Evans, DG (Author) Other; Feliubadalo, L (Author) Other; Foretova, L (Author) Other; Friedman, E (Author) Other; Frost, D (Author) Other; Ganz, PA (Author) Other; Garber, J (Author) Other; Gayther, SA (Author) Other; Gerdes, AM (Author) Other; Godwin, AK (Author) Other; Goldgar, DE (Author) Other; Hahnen, E (Author) Other; Hake, CR (Author) Other; Hamann, U (Author) Other; Hogervorst, FBL (Author) Other; Hooning, MJ (Author) Other; Hopper, JL (Author) Other; Hulick, PJ (Author) Other; Imyanitov, EN (Author) Other; Isaacs, C (Author) Other; Izatt, L (Author) Other; Jakubowska, A (Author) Other; James, PA (Author) Other; Janavicius, R (Author) Other; Jensen, UB (Author) Other; Jiao, Y (Author) Other; John, EM (Author) Other; Joseph, V (Author) Other; Karlan, BY (Author) Other; Kets, CM (Author) Other; Konstantopoulou, I (Author) Other; Kwong, A (Author) Other; Legrand, C (Author) Other; Leslie, G (Author) Other; Lesueur, F (Author) Other; Loud, JT (Author) Other; Lubinski, J (Author) Other; Manoukian, S (Author) Other; McGuffog, L (Author) Other; Miller, A (Author) Other; Gomes, DM (Author) Other; Montagna, M (Author) Other; Mouret Fourme, E (Author) Other; Nathanson, KL (Author) Other; Neuhausen, SL (Author) Other; Nevanlinna, H (Author) Other; Yie, JNY (Author) Other; Olah, E (Author) Other; Olopade, OI (Author) Other; Park, SK (Author) Other; Parsons, MT (Author) Other; Peterlongo, P (Author) Other; Piedmonte, M (Author) Other; Radice, P (Author) Other; Rantala, J (Author) Other; Rennert, G (Author) Other; Risch, HA (Author) Other; Schmutzler, RK (Author) Other; Sharma, P (Author) Other; Simard, J (Author) Other; Singer, CF (Author) Other; Stadler, Z (Author) Other; Stoppa Lyonnet, D (Author) Other; Sutter, C (Author) Other; Tan, YY (Author) Other; Manuel R Teixeira (Author) ICBAS; Teo, SH (Author) Other; Teule, A (Author) Other; Thomassen, M (Author) Other; Thull, DL (Author) Other; Tischkowitz, M (Author) Other; Toland, AE (Author) Other; Tung, N (Author) Other; van Rensburg, EJ (Author) Other; Vega, A (Author) Other; Wappenschmidt, B (Author) Other; Devilee, P (Author) Other; van Asperen, CJ (Author) Other; Bernstein, JL (Author) Other; Offit, K (Author) Other; Easton, DF (Author) Other; Rookus, MA (Author) Other; Chenevix Trench, G (Author) Other; Antoniou, AC (Author) Other; Robson, M (Author) Other; Schmidt, MK (Author) Other

Journal

Title: Genetics in Medicine

Vol. 23

Pages: 1726-1737

ISSN: 1098-3600

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00V-3G8

DOI: 10.1038/s41436-021-01198-7

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12