Abstract
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. 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. 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...Continue Reading
References
Feb 28, 1996·Statistics in Medicine·F E HarrellD B Mark
May 1, 2007·Breast Cancer Research : BCR·Georgia Chenevix-TrenchUNKNOWN CIMBA
Mar 22, 2008·American Journal of Human Genetics·Antonis C AntoniouUNKNOWN CIMBA
Aug 7, 2009·Human Molecular Genetics·Antonis C AntoniouUNKNOWN CIMBA
Oct 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Monika K GraeserRita K Schmutzler
Mar 6, 2010·Breast Cancer Research and Treatment·Dorina M van der KolkJan C Oosterwijk
Dec 2, 2010·Cancer Research·Antonis C AntoniouUNKNOWN CIMBA
Feb 24, 2011·JAMA : the Journal of the American Medical Association·Issa J Dahabreh, David M Kent
Apr 14, 2011·British Journal of Cancer·K MetcalfeS A Narod
Apr 19, 2011·International Journal of Methods in Psychiatric Research·Melissa J AzurPhilip J Leaf
Oct 31, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sarah SawyerPaul A James
Dec 12, 2012·Breast Cancer Research : BCR·Kerstin RhiemRita K Schmutzler
Mar 29, 2013·Nature Genetics·Kyriaki MichailidouDouglas F Easton
May 1, 2013·Journal of the National Cancer Institute·Nasim MavaddatUNKNOWN EMBRACE
Sep 11, 2013·American Journal of Surgery·Ingrid M LizarragaCarol E H Scott-Conner
Apr 10, 2015·Journal of the National Cancer Institute·Nasim MavaddatMontserrat Garcia-Closas
Jan 1, 2014·Breast Cancer Research : BCR·Karoline B KuchenbaeckerUNKNOWN CIMBA
Dec 25, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alexandra J van den BroekMarjanka K Schmidt
Oct 5, 2016·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Christopher I AmosDouglas F Easton
Apr 5, 2017·Journal of the National Cancer Institute·Karoline B KuchenbaeckerAntonis C Antoniou
May 19, 2017·Journal of the National Cancer Institute·Mark E RobsonUNKNOWN WECARE Study Collaborative Group
Jun 21, 2017·JAMA : the Journal of the American Medical Association·Karoline B KuchenbaeckerHåkan Olsson
Sep 19, 2017·International Journal of Cancer. Journal International Du Cancer·Colin B BeggJorge S Reis-Filho
Oct 24, 2017·Nature Genetics·Roger L MilneJacques Simard
Oct 24, 2017·Nature·Kyriaki MichailidouDouglas F Easton
Feb 1, 2018·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Jenna LilyquistFergus J Couch
Mar 1, 2018·Journal of the National Cancer Institute·Mitchell H Gail, Ruth M Pfeiffer
Dec 18, 2018·American Journal of Human Genetics·Nasim MavaddatDouglas F Easton
Dec 24, 2018·The Breast : Official Journal of the European Society of Mastology·Delal AkdenizMaartje J Hooning
Jan 31, 2019·Journal of the National Cancer Institute·Iris KramerMarjanka K Schmidt
Dec 19, 2019·Breast Cancer Research : BCR·Daniele GiardielloMarjanka K Schmidt
Jul 16, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Daniel R BarnesUNKNOWN Consortium of Investigators of Modifiers of BRCA and BRCA2
Aug 2, 2020·Nature Communications·Weang-Kee HoAntonis C Antoniou
Oct 7, 2020·American Journal of Human Genetics·Iris KramerMarjanka K Schmidt