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TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort

  • Bakhuizen, J. J.1
  • Hogervorst, F. B.2
  • Velthuizen, M. E.1
  • Ruijs, M. W.2
  • van Engelen, K.3
  • van Os, T. A.3
  • Gille, J. J.3
  • Collée, M.4
  • van den Ouweland, A. M.4
  • van Asperen, C. J.5
  • Kets, C. M.6
  • Mensenkamp, A. R.6
  • Leter, E. M.7
  • Blok, M. J.7
  • de Jong, M. M.8
  • Ausems, M. G.1
  • 1 University Medical Center Utrecht, Department of Genetics, Utrecht, 3508 AB, The Netherlands , Utrecht (Netherlands)
  • 2 Netherlands Cancer Institute, Family Cancer Clinic, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 3 Amsterdam University Medical Centers, Department of Clinical Genetics, Amsterdam, The Netherlands , Amsterdam (Netherlands)
  • 4 Erasmus University Medical Center, Department of Clinical Genetics, Rotterdam, The Netherlands , Rotterdam (Netherlands)
  • 5 Leiden University Medical Center, Department of Clinical Genetics, Leiden, The Netherlands , Leiden (Netherlands)
  • 6 Radboud University Nijmegen Medical Center, Department of Human Genetics, Nijmegen, The Netherlands , Nijmegen (Netherlands)
  • 7 Maastricht University Medical Center, Department of Clinical Genetics, Maastricht, The Netherlands , Maastricht (Netherlands)
  • 8 University of Groningen, Department of Clinical Genetics, University Medical Center Groningen, Groningen, The Netherlands , Groningen (Netherlands)
Published Article
Familial Cancer
Publication Date
Jan 03, 2019
DOI: 10.1007/s10689-018-00118-0
Springer Nature


Early-onset breast cancer may be due to Li–Fraumeni Syndrome (LFS). Current national and international guidelines recommend that TP53 genetic testing should be considered for women with breast cancer diagnosed before the age of 31 years. However, large studies investigating TP53 mutation prevalence in this population are scarce. We collected nationwide laboratory records for all young breast cancer patients tested for TP53 mutations in the Netherlands. Between 2005 and 2016, 370 women diagnosed with breast cancer younger than 30 years of age were tested for TP53 germline mutations, and eight (2.2%) were found to carry a (likely) pathogenic TP53 sequence variant. Among BRCA1/BRCA2 mutation negative women without a family history suggestive of LFS or a personal history of multiple LFS-related tumours, the TP53 mutation frequency was < 1% (2/233). Taking into consideration that TP53 mutation prevalence was comparable or even higher in some studies selecting patients with breast cancer onset at older ages or HER2-positive breast cancers, raises the question of whether a very early age of onset is an appropriate single TP53 genetic testing criterion.

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