Cost-effectiveness of BRCA1/BRCA2 Variant Reclassification and Recontact for Hereditary Breast and Ovarian Cancer in the United States.

Reclassification of variants of uncertain significance in BRCA1/2 impact clinical management, health outcomes, and healthcare costs, raising questions about cost-effectiveness and optimal timing of reinterpretation. This study evaluated cost-effectiveness of BRCA1/2 variant reclassification strategies and how timing and duration influence outcomes. Using data from two independent commercial genetic testing laboratories, a decision analytic model was developed to simulate lifetime breast and ovarian cancer incidence, quality-adjusted life-years (QALYs), life years, and direct medical costs per 1,000 30-year-old women with prior BRCA1/2 testing. Reclassification strategies were modeled as annual or batches, with perpetual or fixed durations. A data-weighted cost of $200 was applied for reclassification and recontact for impactful reclassifications. Incremental costs were estimated of $63 and $155 per 1,000 women with corresponding QALY gains of 0.0007 and 0.0032, resulting in incremental cost-effectiveness ratios of $86,723 and $48,554 respectively. Most incremental cancer reductions resulted from cascade testing. Batch-based reclassification strategies, particularly 5-year intervals with fixed endpoints, emerged as the most cost-effective. Structured, batch-based reclassification strategies with fixed endpoints are more cost-effective than perpetual schedules. This supports planned reclassification cycles to maximize health benefits and cost-effectiveness, conflicting with research supporting ongoing responsibility for reinterpretation without a defined time limit.