Abstract 162P
Background
About 10-20% of hereditary breast and/or ovarian (HBOC) cancer patients undergoing germline BRCA1/2 genetic testing harbour Variants of Uncertain Significance (VUS). Poor is the knowledge about the prevalence of germline BRCA1/2 VUS in HBOC patients of Southern Italy. Our study is aimed at describing the spectrum of these variants detected in HBOC patients in order to improve the patient’s stratification with the identification of potentially high-risk BRCA variants helpful for patient clinical management.
Methods
874 breast (BC) or ovarian (OC) cancer patients, enrolled from October 2016 to April 2021 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlinico “P. Giaccone” of Palermo, were genetically tested for germline BRCA1/2 variants through Next-Generation Sequencing analysis.
Results
The screening results showed that 639 (73.1%) out of 874 patients were BRCA-wild-type, whereas 67 (7.7%) were carriers of germline BRCA1/2 VUS and 168 (19.2%) harboured germline BRCA1/2 Pathogenic/Likely Pathogenic Variants. Overall, the mutational analysis revealed the presence of 59 different VUS detected in 67 patients, 46 of which affected by BC and 21 by OC. Twenty-one (35.6%) out of 59 variants were located on BRCA1 gene, whereas 38 (64.4%) on BRCA2. We have identified six alterations in BRCA1 and two in BRCA2 with unclear interpretation of clinical significance. Familial anamnesis of a patient harbouring BRCA1-c.3367G>T suggests for this variant a potential of pathogenicity as well as the BRCA1-c.4963T>G identified in three unrelated OC patients.
Conclusions
Understanding clinical significance of germline BRCA1/2 VUS could improve the identification of potentially high-risk variants useful for clinical management of BC/OC patients and family members. Reclassifying these variants could make them useful for predictive, prognostic and preventive purposes in clinical practice.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University Hospital Policlinico “P. Giaccone” of Palermo.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.