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.
Subject(s)
Breast Neoplasms/genetics , Genetic Counseling/standards , Genetic Testing/standards , Li-Fraumeni Syndrome/genetics , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Age Factors , Age of Onset , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , DNA Mutational Analysis , Female , Genetic Counseling/statistics & numerical data , Genetic Predisposition to Disease , Genetic Testing/statistics & numerical data , Germ-Line Mutation , Humans , Li-Fraumeni Syndrome/diagnosis , Li-Fraumeni Syndrome/epidemiology , Medical History Taking , Netherlands/epidemiology , Practice Guidelines as Topic , Retrospective Studies , Young AdultABSTRACT
Germline TP53 mutations are associated with an increased risk of early-onset breast cancer. Traditionally, it was not standard practice to offer TP53 genetic testing due to the low mutation detection rate and limited options regarding preventive screening. Recent guidelines recommend that all women diagnosed with breast cancer before the age of 31, irrespective of family history, should be offered TP53 genetic testing. This study aims to gain more knowledge on the attitudes and experiences among genetics professionals regarding the timing and content of genetic counselling of young breast cancer patients for Li-Fraumeni syndrome (LFS). We conducted a nationwide online survey among genetics professionals who provide cancer genetic counselling in the Netherlands. Fifty-seven professionals completed the questionnaire (response rate overall 54%, clinical geneticists 70%). Most respondents reported that they discuss the option of TP53 genetic testing-simultaneously with BRCA 1/2-during the initial counselling visit, especially in case of referral for treatment-focused genetic counselling. There was a general consensus about ten information items that should be discussed during counselling. Sixty-one percent of genetics professionals did not encounter difficulties in providing genetic counselling for LFS, but a substantial minority (29%) did. This study offers valuable insight, which will be useful for clinical practice. Studies which address young breast cancer patients' attitudes and preferences regarding the timing and content of counselling are warranted to further determine the most appropriate genetic counselling strategy for these women.
