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.

Additional Metadata
Keywords Genetic testing · Li–Fraumeni syndrome · TP53 · Breast cancer · Hereditary
Persistent URL dx.doi.org/10.1007/s10689-018-00118-0, hdl.handle.net/1765/116153
Series VSNU Open Access deal
Journal Familial Cancer
Note corresponding author at UMC Utrecht
Bakhuizen, J.J., Hogervorst, F.B.L, Velthuizen, S.J.C.M, Ruijs, M.W., van Engelen, K, van Os, T.A.M, … Ausems, MG. (2019). TP53 germline mutation testing in early-onset breast cancer: findings from a nationwide cohort. Familial Cancer, 18(2), 273–280. doi:10.1007/s10689-018-00118-0