TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort
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.
KeywordsGenetic testing Li–Fraumeni syndrome TP53 Breast cancer Hereditary
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The Medical Research Ethical Committee concluded that the Medical Research Human Subject Acts (WMO) does not apply.
- 1.Netherlands Comprehensive Cancer Organisation (IKNL) (2016) Dutch cancer Figs. 2016 [Internet]. http://www.cijfersoverkanker.nl/. Accessed May 21 2018
- 5.NABON (2017) Breast Cancer, Dutch Guideline [Internet]. http://www.oncoline.nl/borstkanker. Accessed May 25 2018
- 6.National Comprehensive Cancer Network (2018) NCCN Clinical Practice Guidelines in Oncology: genetic/familial high risk assessment: breast and ovarian (Version 2.2019) [internet]. https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf (registration required). Accessed 7 Nov 2018
- 7.Adank MA, Hes FJ, van Zelst-Stams WAG et al (2015) CHEK2-mutation in Dutch breast cancer families: expanding genetic testing for breast cancer (in Dutch). Ned Tijdschr Geneeskd 159:A8910Google Scholar
- 8.Schneider K, Zelley K, Nichols KE et al (1999) Li–Fraumeni syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al (eds) GeneReviews [Internet]. University of Washington, Seattle, WAGoogle Scholar
- 12.Li FP, Fraumeni JF Jr, Mulvihill JJ et al (1988) A cancer family syndrome in twenty-four kindreds. Cancer Res 48(18):5358–5362Google Scholar
- 13.Birch JM, Hartley AL, Tricker KJ et al (1994) Prevalence and diversity of constitutional mutations in the P53 gene among 21 Li–Fraumeni families. Cancer Res 54(5):1298–1304Google Scholar
- 14.Eeles RA (1995) Germline mutations in the TP53 gene. Cancer Surv 25:101–124Google Scholar
- 17.Renaux-Petel M, Charbonnier F, Thery JC et al (2018) Contribution of de novo and mosaic TP53 mutations to Li–Fraumeni syndrome. J Med Genet 55(3):173–180Google Scholar
- 30.Netherlands Foundation for the Detection of Hereditary Tumours (STOET) and the Dutch Society of Clinical Genetics (VKGN) (2005) Guidelines for the diagnosis and prevention of hereditary cancer predisposition syndromes (in Dutch). Edition 2005Google Scholar
- 31.Netherlands Foundation for the Detection of Hereditary Tumours (STOET) and the Dutch Society of Clinical Genetics (VKGN) (2010) Guidelines for the diagnosis and prevention of hereditary cancer predisposition syndromes (in Dutch). Edition 2010Google Scholar
- 32.Netherlands Foundation for the Detection of Hereditary Tumours (STOET) and the Dutch Society of Clinical Genetics (VKGN) (2017) Guidelines for the diagnosis and prevention of hereditary cancer predisposition syndromes (in Dutch). Edition 2017Google Scholar
- 34.Wevers MR, Aaronson NK, Verhoef S et al (2014) Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial. Br J Cancer 110(4):1081–1087CrossRefGoogle Scholar
- 36.Lee DS, Yoon SY, Looi LM et al (2012) Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients. Breast Cancer Res 14(2):R66. https://doi.org/10.1186/bcr3172 CrossRefGoogle Scholar
- 44.PGD Netherlands (2017) Annual report 2017 [Internet]. https://www.pgdnederland.nl/en/annual-reports. Accessed 7 Nov 2018