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

J J Bakhuizen, 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

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17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalFamilial Cancer
Issue number2
Publication statusPublished - Apr 2019
Externally publishedYes


  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • BRCA1 Protein/genetics
  • BRCA2 Protein/genetics
  • Breast Neoplasms/diagnosis
  • DNA Mutational Analysis
  • Female
  • Genetic Counseling/standards
  • Genetic Predisposition to Disease
  • Genetic Testing/standards
  • Germ-Line Mutation
  • Humans
  • Li-Fraumeni Syndrome/diagnosis
  • Medical History Taking
  • Netherlands/epidemiology
  • Practice Guidelines as Topic
  • Retrospective Studies
  • Tumor Suppressor Protein p53/genetics
  • Young Adult


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