Background: For BRCA1 or BRCA2 mutation carriers, decision analysis indicates that prophylactic surgery or chemoprevention leads to better survival than surveillance alone.
Objective: To evaluate the cost-effectiveness of the preventive strategies that are available to unaffected women carrying a single BRCA1 or BRCA2 mutation with high cancer penetrance.
Design: Markov modeling with Monte Carlo simulations and probabilistic sensitivity analyses.
Data sources: Breast and ovarian cancer incidence and mortality rates, preference ratings, and costs derived from the literature; the Surveillance, Epidemiology, and End Results (SEER) Program; and the Health Care Financing Administration (now the Centers for Medicare & Medicaid Services).
Target population: Unaffected carriers of a single BRCA1 or BRCA2 mutation 35 to 50 years of age.
Time horizon: Lifetime.
Perspective: Health policy, societal.
Interventions: Tamoxifen, oral contraceptives, bilateral salpingo-oophorectomy, mastectomy, both surgeries, or surveillance.
Outcome measures: Cost-effectiveness.
Results of base-case analysis: For mutation carriers 35 years of age, both surgeries (prophylactic bilateral mastectomy and oophorectomy) had an incremental cost-effectiveness ratio over oophorectomy alone of 2352 dollars per life-year for BRCA1 and 100 dollars per life-year for BRCA2. With quality adjustment, oophorectomy dominated all other strategies for BRCA1 and had an incremental cost-effectiveness ratio of 2281 dollars per life-year for BRCA2.
Results of sensitivity analysis: Older age at intervention increased the cost-effectiveness of prophylactic mastectomy for BRCA1 mutation carriers to 73,755 dollars per life-year. Varying the penetrance, mortality rates, costs, discount rates, and preferences had minimal effects on outcomes.
Limitations: Results are dependent on the accuracy of model assumptions.
Conclusion: On the basis of this model, the most cost-effective strategies for BRCA mutation carriers, with and without quality adjustment, were oophorectomy alone and oophorectomy and mastectomy, respectively.