Opportunistic Screening of High-Risk Breast Cancer Variants in Hospital Biobank Setting

Genetic data accumulating in biobanks provide novel possibilities for personalized medicine through opportunistic screening. In this pilot study, we evaluated the applicability and impact of screening pathogenic variants (PVs) of BRCA1, BRCA2, and PALB2 genes predisposing to hereditary breast and ovarian cancer (HBOC), from biobank samples.

PVs of BRCA1, BRCA2, and PALB2 were screened from array-based genotyping data produced in the FinnGen study and returned to Helsinki Biobank (HBB). Samples with suspected variants were validated by sequencing, and novel findings were disclosed to participants who had consented to return of results (RoR). Post-disclosure surveys were conducted to examine participants' experiences and perceptions of receiving genetic results.

Of 103 donors contacted, 71% (n = 73) consented to receiving HBOC risk results. In the cohort of approximately 11,000 HBB donors, 73 carriers of PVs in BRCA1, BRCA2, or PALB2 were identified, representing 0.6% of screened samples. Only 26% (n = 19) of these PVs had been previously identified in healthcare. Among newly identified families, 53% (17/32) met the National Comprehensive Cancer Network criteria for genetic testing. Return of biobank-based screening results led to changes in clinical management in 89% (17/19) of newly identified female PV carriers, with 35% opting for risk-reducing surgery. Survey responses indicated high satisfaction with RoR and perceived personal utility of the information.

Returning actionable genetic biobank findings provides clear clinical benefit and is supported by donors.

Our results demonstrate that array-based genotyping data produced from biobank samples can serve in personalized disease-risk screening and preventive medicine.