Parents' experiences with sequencing of all known pediatric cancer predisposition genes in children with cancer.

PURPOSE: Germline DNA sequencing is increasingly used within pediatric oncology, yet parental experiences remain underexplored. METHODS: Parents of children undergoing cancer predisposition gene panel sequencing (143 genes) were surveyed before and after disclosure of results. Questionnaires assessed knowledge, expectations, worries, satisfaction, and regret. Next to descriptives, linear mixed models and generalized mixed models were utilized to explore factors associated with knowledge and worries. RESULTS: Out of 325 eligible families, 310 parents (176 mothers and 128 fathers of 188 families) completed all after-consent questionnaires whereas 260 parents (150 mothers and 110 fathers of 181 families) completed all after disclosure questionnaires. Most parents hoped their participation would benefit others, although individual hopes were also common. Sequencing-related worries were common, particularly concerning whether their child would get cancer again, cancer risks for family members and psychosocial implications of testing. Parental satisfaction after disclosure was high and regret scores were low. Lower education was associated with lower knowledge levels, whereas foreign-born parents were at increased risk of experiencing worries. CONCLUSION: Germline sequencing of children with cancer is generally well received by their parents. However, careful genetic counseling is essential to ensure that parents are adequately informed and supported throughout the process.

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.

Genetic counselling of young women with breast cancer for Li-Fraumeni syndrome: a nationwide survey on the experiences and attitudes of genetics professionals.

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.