1. 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
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Lakeman, Inge MM, van den Broek, Alexandra J, Vos, Juliën AM, Barnes, Daniel R, Adlard, Julian, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Arun, Banu K, Balmaña, Judith, Barrowdale, Daniel, Benitez, Javier, Borg, Ake, Caldés, Trinidad, Caligo, Maria A, Chung, Wendy K, Claes, Kathleen BM, Collée, J Margriet, Couch, Fergus J, Daly, Mary B, Dennis, Joe, Dhawan, Mallika, Domchek, Susan M, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Foretova, Lenka, Friedman, Eitan, Frost, Debra, Ganz, Patricia A, Garber, Judy, Gayther, Simon A, Gerdes, Anne-Marie, Godwin, Andrew K, Goldgar, David E, Hahnen, Eric, Hake, Christopher R, Hamann, Ute, Hogervorst, Frans BL, Hooning, Maartje J, Hopper, John L, Hulick, Peter J, Imyanitov, Evgeny N, Isaacs, Claudine, Izatt, Louise, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Jiao, Yue, John, Esther M, Joseph, Vijai, Karlan, Beth Y, Kets, Carolien M, Konstantopoulou, Irene, Kwong, Ava, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Loud, Jennifer T, Lubiński, Jan, Manoukian, Siranoush, McGuffog, Lesley, Miller, Austin, Gomes, Denise Molina, Montagna, Marco, Mouret-Fourme, Emmanuelle, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Olah, Edith, Olopade, Olufunmilayo I, Park, Sue K, Parsons, Michael T, Peterlongo, Paolo, Piedmonte, Marion, Radice, Paolo, Rantala, Johanna, Rennert, Gad, Risch, Harvey A, Schmutzler, Rita K, Sharma, Priyanka, Simard, Jacques, Singer, Christian F, Stadler, Zsofia, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teo, Soo Hwang, Teulé, Alex, Thomassen, Mads, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tung, Nadine, van Rensburg, Elizabeth J, and Vega, Ana
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Biological Sciences ,Genetics ,Cancer ,Breast Cancer ,Prevention ,Aging ,2.1 Biological and endogenous factors ,Aetiology ,Adult ,BRCA1 Protein ,BRCA2 Protein ,Breast Neoplasms ,Female ,Genetic Predisposition to Disease ,Heterozygote ,Humans ,Mutation ,Retrospective Studies ,Risk Factors ,GEMO Study Collaborators ,EMBRACE Collaborators ,OCGN Investigators ,HEBON Investigators ,KconFab Investigators ,Clinical Sciences ,Genetics & Heredity - Abstract
PurposeTo 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.MethodsWe 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.ResultsFor 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
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- 2021