Abstract 1709P
Background
Hereditary cancer predisposition syndromes are responsible for approximately 5-10% of all diagnosed cancer cases. Identification of genetic predisposition using germline testing, is usually followed by targeted variant testing in family members, ensuring a cost-effective approach for identifying high-risk individuals. Consequently, this has significant implications for treatment decisions, risk-reducing interventions, and cancer screening and prevention.
Methods
The aim of this study is to examine the clinical use and implementation of cascade family testing (CFT) in the families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs). Germline sequencing was carried out with NGS technology using a 43-gene panel and cascade testing was performed with Sanger sequencing or MLPA.
Results
In a cohort of 1785 patients with breast cancer, PVs/LPVs were found in 362 patients (20.3%). In specific, 52.2%, 25.1%, and 22.7% of positive patients had findings in high-, moderate- and low- penetrance cancer susceptibility genes, respectively. Although, CFT was advised in all families, 117 individuals from 113 families (31.2%) continued with genetic testing. The mean ages of probands and first-degree relatives tested were 46 and 40 years (p<0.0001), respectively. Of the first-degree relatives who underwent CFT, 70% were female and the 105/117 (89.7%) were asymptomatic. Among the 117 tested individuals, 42.7%, 36.7% and 20.6% were offspring, siblings, and parents of probands, respectively. In total, the familial PV/LPV was detected in 53.0% (62/117) of first-degree relatives tested. Our data suggest that CFT was mostly undertaken (91.4%) in families with positive findings in high-risk genes, although these represent only 55.0% of initial families with PV/LPV in high-risk genes.
Conclusions
Our results underline the fact that CFT is underutilized, even in families with PVs/LPVs in high-risk genes. However, cascade testing can be a powerful tool for primary cancer prevention towards the identification of at-risk family members. Additional efforts should be targeted to the implementation of genetic counseling approaches leading to better family education and communication of genetic testing results.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.