Cascade testing in Italian Hereditary Breast Ovarian Cancer families: a missed opportunity for cancer prevention?

Abstract

Abstract Healthy carriers of BRCA1/2 pathogenic variants (PVs) may benefit from risk-reducing measures of proven efficacy. The main approach to identify these individuals is cascade testing, and strategies to support this complex process are under investigation. In Italy, cascade testing has received little attention; therefore, we analyzed the uptake and characteristics of BRCA1/2 cascade testing in families diagnosed with HBOC at two Italian genetics centers between 2017 and 2019. All consanguineous family members who were older than 18 years of age at data collection time and who could be involved in the first step of cascade testing (i.e., all the living relatives closest to the proband) were included. In addition to first-degree relatives, individuals who were second-, third- or fourth-degree relatives were included if the closest relative(s) was/were deceased. Overall, 213 families were included (103, Genoa; 110, Bologna). Most probands were women affected by breast and/or ovarian cancer (86.4%, Genoa; 84.5%, Bologna), and the branch segregating the PV was known/suspected in most families (62.1%, Genoa; 60.9%, Bologna). Overall, the uptake of cascade testing was low (22%, Genoa; 16%, Bologna). It was associated with female gender (OR = 5.74, Genoa; OR = 3.33, Bologna), age < 30 years (OR = 10.31, Genoa; OR = 4.84, Bologna), first-degree relationship with the proband (OR = 20,94, Genoa; OR = 12.44, Bologna) and segregation of the PV in the paternal branch (OR = 2.90, Genoa; OR = 2.54, Bologna). These real-world data may be important to inform the design and implementation of strategies aimed at improving the uptake of HBOC cascade testing in Italy.