BRCA cascade counselling and testing in Italy: current position and future directions

Abstract

Background: Genetic testing has led to a considerable enhancement in the ability to identify individuals at risk of Hereditary Breast and Ovarian Cancer syndrome related to BRCA1/2 pathogenic variants, thus necessitating personalised prevention programs. However, barriers related to intrafamilial communication, privacy regulations, and genetic information dissemination hinder preventive care, particularly in Italy, where legal constraints limit the disclosure of genetic risks to at-risk relatives. This study examines the relationship between BRCA1/2 carriers' communication challenges and three factors: cancer status, comprehension of genetic information, and the genetic counseling pathway accessed (Traditional Genetic Counseling, TGC vs. Mainstream Cancer Genetics, MCG).

Methods: This multicenter, prospective, observational study included 277 BRCA1/2 carriers (probands and relatives) aged 18-80 from various Italian centers. Participants completed a sociodemographic form, a self-administered survey, and psychological assessments (Impact of Event Scale, IES and Distress Thermometer, DT). Categorical variables were compared using Pearson's Chi-squared test or Fisher's exact test based on sample size and expected frequencies, whereas continuous variables were analyzed using the Wilcoxon rank-sum test because of non-normal data distribution.

Results: Among the 277 carriers (115 probands, 162 relatives), 79.4% received TGC and 20.6% MCG. The cancer prevalence was higher in probands (83%) than in relatives (22%). The probands exhibited greater psychological distress (higher IES and DT scores), and cancer-affected relatives had higher distress levels than healthy relatives (p = 0.008). While no severe psychological distress or PTSD was found, distress was more associated with cancer diagnosis than genetic status. Genetic comprehension was significantly higher in relatives (p = 0.007) and in those who underwent TGC compared to MCG (p < 0.001). TGC carriers also better understood genetic risks and management strategies (p < 0.001).

Conclusions: Psychological distress and genetic comprehension significantly influenced the communication. TGC enhances understanding more effectively than MCG, highlighting the need for tailored support for both carriers and healthcare professionals to improve cascade counseling and testing rates, and cancer prevention. As we look into the future, we need to critically approach MCG, and determine how to address carriers understanding and prevention needs and reincorporate a more comprehensive genetic risk assessment into the MCG model.

Keywords: BRCA1/2; Cascade genetic counselling and testing; Communication; Mainstream cancer genetics; Psychological distress; Traditional genetic counselling.