Comparative Analysis of BRCA Pathogenic Variant Detection in a Real-World Setting: Population Screening Versus Oncogenetic Clinics

真实世界环境下 BRCA 致病变异检测的比较分析:人群筛查与肿瘤遗传诊所

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Abstract

PURPOSE: Israel has pioneered population-wide screening (PS) for BRCA 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. METHODS: A cohort study conducted at BRCA 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 BRCA1/2 PV carriers: PS carriers received only post-test genetic counseling, whereas OC carriers received both pre- and post-test counseling. RESULTS: We identified 352 carriers: 202 PS and 150 OC. Sociodemographic characteristics were similar. PS carriers harbored more BRCA2-PVs (62.9% v 48.7%, P = .001) rather than BRCA1-PVs, and fewer had suggestive family history (FH) (40.4% v 61%, P < .001). In univariate analysis, both groups reported satisfaction with pretest information. PS carriers reported lower satisfaction with result delivery: (3.3 ± 1.3 v 3.9 ± 1.2 [scale 1-5]; P = .001) and health decisions: (24.6 ± 3.9 v 25.9 ± 3.6 [scale 6-30]; P = .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: BRCA1 ≥40 years: 74.1% versus 85.7%, BRCA2 ≥45 years: 81.4% versus 63.5%, respectively. CONCLUSION: In a real-world setting, PS identified carriers with less FH and more BRCA2-PVs. PS was associated with favorable psychosocial outcomes and high RR-BSO uptake. The process requires refinement and long-term evaluation.

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