Cost-effectiveness of BRCA1/BRCA2 variant reclassification and recontact for hereditary breast and ovarian cancer in...

Reclassification of variants of uncertain significance in BRCA1/2 affects clinical management, health outcomes, and health care costs, raising questions about cost-effectiveness and optimal timing of reinterpretation. This study evaluated the cost-effectiveness of BRCA1/2 variant reclassification strategies and how timing and duration influence outcomes.

Using data from 2 independent commercial genetic testing laboratories, a decision-analytic model was developed to simulate lifetime breast and ovarian cancer incidence, quality-adjusted life-years, life-years, and direct medical costs per 1000 30-year-old women with prior BRCA1/2 testing. Reclassification strategies were modeled as annual or in 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 at $63 and $155 per 1000 women, with corresponding quality-adjusted life-year 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 end points, emerged as the most cost-effective.

Structured, batch-based reclassification strategies with fixed end points are more cost-effective than perpetual schedules. This supports planned reclassification cycles to maximize health benefits and cost-effectiveness, which conflicts with research supporting ongoing responsibility for reinterpretation without a defined time limit.