Comparative Analysis of <i>BRCA</i> Pathogenic Variant Detection in a Real-World Setting: Population Screening Versus Oncogenetic Clinics.

Abstract

Israel has pioneered population-wide screening (PS) for <i>BRCA</i> pathogenic variants (PVs). We aimed to compare psychosocial aspects and outcomes of carriers identified through PS versus via oncogenetic clinics (OC) in a real-world setting. A cohort study conducted at <i>BRCA</i> high-risk surveillance clinic in Shaare Zedek Medical Center Jerusalem, Israel (9.2021-5.2024). Data were obtained from electronic medical records and self-reported questionnaires. The study included newly identified unaffected female <i>BRCA1/2</i> PV carriers: PS carriers received only post-test genetic counseling, whereas OC carriers received both pre- and post-test counseling. We identified 352 carriers: 202 PS and 150 OC. Sociodemographic characteristics were similar. PS carriers harbored more <i>BRCA2</i>-PVs (62.9% <i>v</i> 48.7%, <i>P</i> = .001) rather than <i>BRCA1</i>-PVs, and fewer had suggestive family history (FH) (40.4% <i>v</i> 61%, <i>P</i> < .001). In univariate analysis, both groups reported satisfaction with pretest information. PS carriers reported lower satisfaction with result delivery: (3.3 ± 1.3 <i>v</i> 3.9 ± 1.2 [scale 1-5]; <i>P</i> = .001) and health decisions: (24.6 ± 3.9 <i>v</i> 25.9 ± 3.6 [scale 6-30]; <i>P</i> = .014). However, testing mode was not predictive of psychosocial outcomes in multivariate analysis. Risk-reducing bilateral salpingo-oophorectomy (RR-BSO) rates at recommended age were similar in PS and OC: <i>BRCA1</i> ≥40 years: 74.1% versus 85.7%, <i>BRCA2</i> ≥45 years: 81.4% versus 63.5%, respectively. In a real-world setting, PS identified carriers with less FH and more <i>BRCA2</i>-PVs. PS was associated with favorable psychosocial outcomes and high RR-BSO uptake. The process requires refinement and long-term evaluation.