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
Creators: name: Lakeman, Inge M. M.
name: Van Den Broek, Alexandra J.
name: Vos, Juliën A. M.
name: Barnes, Daniel R.
name: Adlard, Julian
name: Andrulis, Irene L.
name: Arason, Adalgeir
name: Arnold, Norbert
name: Arun, Banu K.
name: Balmaña, Judith
name: Barrowdale, Daniel
name: Benitez, Javier
name: Borg, Ake
name: Caldés, Trinidad
name: Caligo, Maria A.
name: Chung, Wendy K.
name: Claes, Kathleen B. M.
name: Collée, J. Margriet
name: Couch, Fergus J.
name: Daly, Mary B.
name: Dennis, Joe
name: Dhawan, Mallika
name: Domchek, Susan M.
name: Eeles, Ros
name: Engel, Christoph
name: Evans, D. Gareth
name: Feliubadaló, Lidia
name: Foretova, Lenka
name: Friedman, Eitan
name: Frost, Debra
name: Ganz, Patricia A.
name: Garber, Judy
name: Gayther, Simon A.
name: Gerdes, Anne-Marie
name: Godwin, Andrew K.
name: Goldgar, David E.
name: Hahnen, Eric
name: Hake, Christopher R.
name: Hamann, Ute
name: Hogervorst, Frans B. L.
name: Hooning, Maartje J.
name: Hopper, John L.
name: Hulick, Peter J.
name: Imyanitov, Evgeny N.
name: Isaacs, Claudine
name: Izatt, Louise
name: Jakubowska, Anna
name: James, Paul A.
name: Janavicius, Ramunas
name: Jensen, Uffe Birk
name: Jiao, Yue
name: John, Esther M.
name: Joseph, Vijai
name: Karlan, Beth Y.
name: Kets, Carolien M.
name: Konstantopoulou, Irene
name: Kwong, Ava
name: Legrand, Clémentine
name: Leslie, Goska
name: Lesueur, Fabienne
name: Loud, Jennifer T.
name: Lubiński, Jan
name: Manoukian, Siranoush
name: McGuffog, Lesley
name: Miller, Austin
name: Gomes, Denise Molina
name: Montagna, Marco
name: Mouret-Fourme, Emmanuelle
name: Nathanson, Katherine L.
name: Neuhausen, Susan L.
name: Nevanlinna, Heli
name: Yie, Joanne Ngeow Yuen
name: Olah, Edith
name: Olopade, Olufunmilayo I.
name: Park, Sue K.
name: Parsons, Michael T.
name: Peterlongo, Paolo
name: Piedmonte, Marion
name: Radice, Paolo
name: Rantala, Johanna
name: Rennert, Gad
name: Risch, Harvey A.
name: Schmutzler, Rita K.
name: Sharma, Priyanka
name: Simard, Jacques
name: Singer, Christian F.
name: Stadler, Zsofia
name: Stoppa-Lyonnet, Dominique
name: Sutter, Christian
name: Tan, Yen Yen
name: Teixeira, Manuel R.
name: Teo, Soo Hwang
name: Teulé, Alex
name: Thomassen, Mads
name: Thull, Darcy L.
name: Tischkowitz, Marc
name: Toland, Amanda E.
name: Tung, Nadine
name: Van Rensburg, Elizabeth J.
name: Vega, Ana
name: Wappenschmidt, Barbara
name: Devilee, Peter
name: Van Asperen, Christi J.
name: Bernstein, Jonine L.
name: Offit, Kenneth
name: Easton, Douglas F.
name: Rookus, Matti A.
name: Chenevix-Trench, Georgia
name: Antoniou, Antonis C.
name: Robson, Mark
name: Schmidt, Marjanka K.
name: Barouk-Simonet, Emmanuelle
name: Belotti, Muriel
name: Berthet, Pascaline
name: Bignon, Yves-Jean
name: Bonadona, Valérie
name: Bressac-De Paillerets, Brigitte
name: Buecher, Bruno
name: Caputo, Sandrine
name: Caron, Olivier
name: Castera, Laurent
name: Caux-Moncoutier, Virginie
name: Colas, Chrystelle
name: Collonge-Rame, Marie-Agnès
name: Coupier, Isabelle
name: De Pauw, Antoine
name: Delnatte, Capucine
name: Elan, Camille
name: Faivre, Laurence
name: Ferrer, Sandra Fert
name: Gauthier-Villars, Marion
name: Gesta, Paul
name: Giraud, Sophie
name: Golmard, Lisa
name: Houdayer, Claude
name: Lasset, Christine
name: Laurent, Maïté
name: Leroux, Dominique
name: Longy, Michel
name: Mari, Véronique
name: Mazoyer, Sylvie
name: Mebirouk, Noura
name: Mortemousque, Isabelle
name: Prieur, Fabienne
name: Pujol, Pascal
name: Saule, Claire
name: Schuster, Helene
name: Sevenet, Nicolas
name: Sobol, Hagay
name: Sokolowska, Johanna
name: Venat-Bouvet, Laurence
name: Ahmed, Munaza
name: Barwell, Julian
name: Brady, Angela
name: Brennan, Paul
name: Brewer, Carole
name: Cook, Jackie
name: Davidson, Rosemarie
name: Donaldson, Alan
name: Dunning, Alison M.
name: Eason, Jacqueline
name: Eccles, Diana M.
name: Gregory, Helen
name: Hanson, Helen
name: Harrington, Patricia A.
name: Henderson, Alex
name: Hodgson, Shirley
name: Kennedy, M. John
name: Lalloo, Fiona
name: Miller, Clare
name: Morrison, Patrick J.
name: Ong, Kai-Ren
name: O’Shaughnessy-Kirwan, Aoife
name: Perkins, Jo
name: Porteous, Mary E.
name: Rogers, Mark T.
name: Side, Lucy E.
name: Snape, Katie
name: Walker, Lisa
name: Glendon, Gord
name: Mulligan, Anna Marie
name: Aalfs, Cora M.
name: Adank, Muriel A.
name: Ausems, Margreet G. E. M.
name: Blok, Marinus J.
name: Gómez Garcia, Encarna B.
name: Heemskerk-Gerritsen, Bernadette A. M.
name: Hollestelle, Antoinette
name: Jager, Agnes
name: Koppert, Linetta B.
name: Koudijs, Marco
name: Kriege, Mieke
name: Meijers-Heijboer, Hanne E. J.
name: Mensenkamp, Arjen R.
name: Mooij, Thea M.
name: Oosterwijk, Jan C.
name: Van Den Ouweland, Ans M. W.
name: Van Der Baan, Frederieke H.
name: Van Der Hout, Annemieke H.
name: Van Der Kolk, Lizet E.
name: Van Der Luijt, Rob B.
name: Van Deurzen, Carolien H. M.
name: Van Doorn, Helena C.
name: Van Engelen, Klaartje
name: Van Hest, Liselotte P.
name: Van Os, Theo A. M.
name: Verhoef, Senno
name: Vogel, Maartje J.
name: Wijnen, Juul T.
name: Beesley, Jonathan
name: Fox, Stephen
name: Holland, Helene
name: Phillips, Kelly-Anne
name: Spurdle, Amanda B.
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Article
article

description: Abstract: 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 &lt; 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.