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Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

  • Muranen, Taru A.1
  • Khan, Sofia1, 2
  • Fagerholm, Rainer1
  • Aittomäki, Kristiina1
  • Cunningham, Julie M.3
  • Dennis, Joe4
  • Leslie, Goska4
  • McGuffog, Lesley4
  • Parsons, Michael T.5
  • Simard, Jacques6
  • Slager, Susan7
  • Soucy, Penny6
  • Easton, Douglas F.4, 8
  • Tischkowitz, Marc9, 10
  • Spurdle, Amanda B.5
  • Schmutzler, Rita K.11, 12
  • Wappenschmidt, Barbara11, 12
  • Hahnen, Eric11, 12
  • Hooning, Maartje J.13
  • Singer, Christian F.14
  • And 21 more
  • 1 Helsinki University Hospital, Helsinki, Finland , Helsinki (Finland)
  • 2 University of Turku and Åbo Akademi University, Turku Bioscience Centre, Turku, Finland , Turku (Finland)
  • 3 Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, USA , Rochester (United States)
  • 4 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK , Cambridge (United Kingdom)
  • 5 QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, QLD, Australia , Brisbane (Australia)
  • 6 CHU de Quebec Research Center, Genomics Center, Québec City, QC, Canada , Québec City (Canada)
  • 7 Mayo Clinic, Department of Health Sciences Research, Rochester, MN, USA , Rochester (United States)
  • 8 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK , Cambridge (United Kingdom)
  • 9 McGill University, Program in Cancer Genetics, Departments of Human Genetics and Oncology, Montréal, QC, Canada , Montréal (Canada)
  • 10 University of Cambridge, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK , Cambridge (United Kingdom)
  • 11 Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Hereditary Breast and Ovarian Cancer, Cologne, Germany , Cologne (Germany)
  • 12 University of Cologne, Center for Molecular Medicine Cologne (CMMC), Cologne, Germany , Cologne (Germany)
  • 13 Erasmus MC Cancer Institute, Department of Medical Oncology, Family Cancer Clinic, Rotterdam, The Netherlands , Rotterdam (Netherlands)
  • 14 Medical University of Vienna, Dept of OB/GYN and Comprehensive Cancer Center, Vienna, Austria , Vienna (Austria)
  • 15 Odense University Hospital, Department of Clinical Genetics, Odence C, Denmark , Odence C (Denmark)
  • 16 Aalborg University Hospital, Molecular Diagnostics, Aalborg, Denmark , Aalborg (Denmark)
  • 17 Aalborg University, Dept of Clinical Medicine, Aalborg, Denmark , Aalborg (Denmark)
  • 18 Perelman School of Medicine at the University of Pennsylvania, Department of Medicine, Abramson Cancer Center, Philadelphia, PA, USA , Philadelphia (United States)
  • 19 ICO-IDIBELL (Bellvitge Biomedical Research Institute, Catalan Institute of Oncology), CIBERONC, Molecular Diagnostic Unit, Hereditary Cancer Program, Barcelona, Spain , Barcelona (Spain)
  • 20 Rigshospitalet, Copenhagen University Hospital, Center for Genomic Medicine, Copenhagen, Denmark , Copenhagen (Denmark)
  • 21 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada , Toronto (Canada)
  • 22 University of Toronto, Department of Molecular Genetics, Toronto, ON, Canada , Toronto (Canada)
  • 23 Portuguese Oncology Institute, Department of Genetics, Porto, Portugal , Porto (Portugal)
  • 24 University of Porto, Biomedical Sciences Institute (ICBAS), Porto, Portugal , Porto (Portugal)
  • 25 Peter MacCallum Cancer Center, Parkville Familial Cancer Centre, Melbourne, VIC, Australia , Melbourne (Australia)
  • 26 The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia , Melbourne (Australia)
  • 27 Dana-Farber Cancer Institute, Cancer Risk and Prevention Clinic, Boston, MA, USA , Boston (United States)
  • 28 City of Hope, Clinical Cancer Genomics, Duarte, CA, USA , Duarte (United States)
  • 29 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland , Szczecin (Poland)
  • 30 Pomeranian Medical University, Independent Laboratory of Molecular Biology and Genetic Diagnostics, Szczecin, Poland , Szczecin (Poland)
  • 31 National Centre for Scientific Research ‘Demokritos’, Molecular Diagnostics Laboratory, INRASTES, Athens, Greece , Athens (Greece)
  • 32 Stanford Cancer Institute, Stanford University School of Medicine, Department of Medicine, Division of Oncology, Stanford, CA, USA , Stanford (United States)
  • 33 Monash University, Precision Medicine, School of Clinical Sciences at Monash Health, Clayton, VIC, Australia , Clayton (Australia)
  • 34 The University of Melbourne, Department of Clinical Pathology, Melbourne, VIC, Australia , Melbourne (Australia)
  • 35 The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Division of Molecular Pathology, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 36 The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Division of Psychosocial Research and Epidemiology, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 37 Örebro University Hospital, Department of Oncology, Örebro, Sweden , Örebro (Sweden)
Published Article
npj Breast Cancer
Nature Publishing Group UK
Publication Date
Sep 10, 2020
DOI: 10.1038/s41523-020-00185-6
Springer Nature


Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03–6.30, P = 3.1 × 10−9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics.

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