• Kristin Anderson, Judith S Jacobson, Daniel F Heitjan, Zivin Joshua Graff JG, Dawn Hershman, Alfred I Neugut, and Victor R Grann.
• Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Joseph L. Mailman School of Public Health, Columbia University, and New York Presbyterian Hospital, New York, New York 10032, USA.
• Ann. Intern. Med. 2006 Mar 21; 144 (6): 397-406.

BackgroundFor BRCA1 or BRCA2 mutation carriers, decision analysis indicates that prophylactic surgery or chemoprevention leads to better survival than surveillance alone.ObjectiveTo 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.DesignMarkov modeling with Monte Carlo simulations and probabilistic sensitivity analyses.Data SourcesBreast 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 PopulationUnaffected carriers of a single BRCA1 or BRCA2 mutation 35 to 50 years of age.Time HorizonLifetime.PerspectiveHealth policy, societal.InterventionsTamoxifen, oral contraceptives, bilateral salpingo-oophorectomy, mastectomy, both surgeries, or surveillance.Outcome MeasuresCost-effectiveness.Results Of Base Case AnalysisFor 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 AnalysisOlder 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.LimitationsResults are dependent on the accuracy of model assumptions.ConclusionOn 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.

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