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
Archive ouverte
Lakeman, Inge | van den Broek, Alexandra | Vos, Juliën | Barnes, Daniel | Adlard, Julian | Andrulis, Irene | Arason, Adalgeir | Arnold, Norbert | Arun, Banu | Balmaña, Judith | Barrowdale, Daniel | Benitez, Javier | Borg, Ake | Caldés, Trinidad | Caligo, Maria | Chung, Wendy | Claes, Kathleen | Collée, J Margriet | Couch, Fergus | Daly, Mary | Dennis, Joe | Dhawan, Mallika | Domchek, Susan | Eeles, Ros | Engel, Christoph | Evans, D Gareth | Feliubadaló, Lidia | Foretova, Lenka | Friedman, Eitan | Frost, Debra | Ganz, Patricia | Garber, Judy | Gayther, Simon | Gerdes, Anne-Marie | Godwin, Andrew | Goldgar, David | Hahnen, Eric | Hake, Christopher | Hamann, Ute | Hogervorst, Frans | Hooning, Maartje | Hopper, John | Hulick, Peter | Imyanitov, Evgeny | Isaacs, Claudine | Izatt, Louise | Jakubowska, Anna | James, Paul | Janavicius, Ramunas | Jensen, Uffe Birk | Jiao, Yue | John, Esther | Joseph, Vijai | Karlan, Beth | Kets, Carolien | Konstantopoulou, Irene | Kwong, Ava | Legrand, Clémentine | Leslie, Goska | Lesueur, Fabienne | Loud, Jennifer | Lubiński, Jan | Manoukian, Siranoush | Mcguffog, Lesley | Miller, Austin | Gomes, Denise Molina | Montagna, Marco | Mouret-Fourme, Emmanuelle | Nathanson, Katherine | Neuhausen, Susan | Nevanlinna, Heli | Yie, Joanne Ngeow Yuen | Olah, Edith | Olopade, Olufunmilayo | Park, Sue | Parsons, Michael | Peterlongo, Paolo | Piedmonte, Marion | Radice, Paolo | Rantala, Johanna | Rennert, Gad | Risch, Harvey | Schmutzler, Rita | Sharma, Priyanka | Simard, Jacques | Singer, Christian | Stadler, Zsofia | Stoppa-Lyonnet, Dominique | Sutter, Christian | Tan, Yen Yen | Teixeira, Manuel | Teo, Soo Hwang | Teulé, Alex | Thomassen, Mads | Thull, Darcy | Tischkowitz, Marc | Toland, Amanda | Tung, Nadine | van Rensburg, Elizabeth | Vega, Ana | Wappenschmidt, Barbara | Devilee, Peter | van Asperen, Christi | Bernstein, Jonine | Offit, Kenneth | Easton, Douglas | Rookus, Matti | Chenevix-Trench, Georgia | Antoniou, Antonis | Robson, Mark | Schmidt, Marjanka | Claes, Kathleen B.M. | Barouk-Simonet, Emmanuelle | Belotti, Muriel | Berthet, Pascaline | Bignon, Yves-Jean | Bonadona, Valérie | Bressac-de Paillerets, Brigitte | 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 | Ahmed, Munaza | Barwell, Julian | Brady, Angela | Brennan, Paul | Brewer, Carole | Cook, Jackie | Davidson, Rosemarie | Donaldson, Alan | Dunning, Alison | Eason, Jacqueline | Eccles, Diana | Gregory, Helen | Hanson, Helen | Harrington, Patricia | Henderson, Alex | Hodgson, Shirley | Kennedy, M. John | Lalloo, Fiona | Miller, Clare | Morrison, Patrick | Ong, Kai-Ren | O’shaughnessy-Kirwan, Aoife | Perkins, Jo | Porteous, Mary | Rogers, Mark | Side, Lucy | Snape, Katie | Walker, Lisa | Glendon, Gord | Mulligan, Anna Marie | Aalfs, Cora | Adank, Muriel | Ausems, Margreet G.E.M. | Blok, Marinus | Gómez Garcia, Encarna | Heemskerk-Gerritsen, Bernadette A.M. | Hollestelle, Antoinette | Jager, Agnes | Koppert, Linetta | Koudijs, Marco | Kriege, Mieke | Meijers-Heijboer, Hanne E.J. | Mensenkamp, Arjen | Mooij, Thea | Oosterwijk, Jan | van den Ouweland, Ans M.W. | van Der Baan, Frederieke | van Der Hout, Annemieke | van Der Kolk, Lizet | van Der Luijt, Rob | van Deurzen, Carolien H.M. | van Doorn, Helena | van Engelen, Klaartje | van Hest, Liselotte | van Os, Theo A.M. | Verhoef, Senno | Vogel, Maartje | Wijnen, Juul | Beesley, Jonathan | Fox, Stephen | Holland, Helene | Phillips, Kelly-Anne | Spurdle, Amanda
Edité par
CCSD ; Nature Publishing Group -
International audience.
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.
