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

  • J. J. BakhuizenEmail author
  • F. B. Hogervorst
  • M. E. Velthuizen
  • M. W. Ruijs
  • K. van Engelen
  • T. A. van Os
  • J. J. Gille
  • M. Collée
  • A. M. van den Ouweland
  • C. J. van Asperen
  • C. M. Kets
  • A. R. Mensenkamp
  • E. M. Leter
  • M. J. Blok
  • M. M. de Jong
  • M. G. Ausems
Original Article

Abstract

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.

Keywords

Genetic testing Li–Fraumeni syndrome TP53 Breast cancer Hereditary 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The Medical Research Ethical Committee concluded that the Medical Research Human Subject Acts (WMO) does not apply.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • J. J. Bakhuizen
    • 1
    Email author
  • F. B. Hogervorst
    • 2
  • M. E. Velthuizen
    • 1
  • M. W. Ruijs
    • 2
  • K. van Engelen
    • 3
  • T. A. van Os
    • 3
  • J. J. Gille
    • 3
  • M. Collée
    • 4
  • A. M. van den Ouweland
    • 4
  • C. J. van Asperen
    • 5
  • C. M. Kets
    • 6
  • A. R. Mensenkamp
    • 6
  • E. M. Leter
    • 7
  • M. J. Blok
    • 7
  • M. M. de Jong
    • 8
  • M. G. Ausems
    • 1
  1. 1.Department of GeneticsUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Family Cancer ClinicNetherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department of Clinical GeneticsAmsterdam University Medical CentersAmsterdamThe Netherlands
  4. 4.Department of Clinical GeneticsErasmus University Medical CenterRotterdamThe Netherlands
  5. 5.Department of Clinical GeneticsLeiden University Medical CenterLeidenThe Netherlands
  6. 6.Department of Human GeneticsRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  7. 7.Department of Clinical GeneticsMaastricht University Medical CenterMaastrichtThe Netherlands
  8. 8.Department of Clinical Genetics, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands

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