Cost-Effectiveness of Preventive Strategies for Women with a BRCA1 or a BRCA2 Mutation

21 March 2006 | Volume 144 Issue 6 | Pages 397-406

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 per life-year for BRCA1 and $100 per life-year for BRCA2. With quality adjustment, oophorectomy dominated all other strategies for BRCA1 and had an incremental cost-effectiveness ratio of $2281 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 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.

Editors' Notes Context Recent research has provided more precise estimates of the age-specific incidence of ovarian and breast cancer in carriers of BRCA mutations. These data will help define the value of prophylactic surgery for these women. Content For BRCA2 carriers, the authors' decision model shows that combined prophylactic surgery (mastectomy and bilateral salpingo-oophorectomy) was very cost-effective relative to oophorectomy alone. Both strategies dominated (were less costly and were more effective) surveillance, prophylactic mastectomy alone, or chemoprevention. For BRCA1 carriers, oophorectomy dominated all other strategies. Limitations The model uses observational study data and expert opinion. Implications Oophorectomy alone or in combination with mastectomy is the most cost-effective strategy for BRCA mutation carriers. —The Editors

 

Author and Article Information

From the 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, and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Grant Support: By a research scholar grant from the American Cancer Society (RSGHP-03-166-01-PBP). Drs. Hershman and Neugut are the recipients of a K07 Award (CA-95597) and a K05 Award (CA89155), respectively, from the National Cancer Institute.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Victor R. Grann, MD, MPH, Mailman School of Public Health, Columbia University, Room 734, 722 West 168th Street, New York, NY 10032; e-mail, VRG2{at}columbia.edu.

Current Author Addresses: Ms. Anderson: Medical School Duluth, University of Minnesota, Duluth, School of Medicine 113, 1035 University Drive, Duluth, MN 55812-3031.

Drs. Jacobson and Graff Zivin: Columbia University, 722 West 168th Street, New York, NY 10032.

Dr. Heitjan: Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-6021.

Dr. Hershman: Herbert Irving Comprehensive Cancer Center, 161 Fort Washington Avenue, Room AP-1068, New York, NY 10032.

Drs. Neugut and Grann: Mailman School of Public Health, Columbia University, Room 734, 722 West 168th Street, New York, NY 10032.

Author Contributions: Conception and design: K. Anderson, D.F. Heitjan, J. Graff Zivin, D. Hershman, A.I. Neugut, V.R. Grann.

Analysis and interpretation of the data: K. Anderson, J.S. Jacobson, D.F. Heitjan, D. Hershman, A.I. Neugut, V.R. Grann.

Drafting of the article: K. Anderson, J.S. Jacobson, D. Hershman, V.R. Grann.

Critical revision of the article for important intellectual content: K. Anderson, J.S. Jacobson, D.F. Heitjan, J. Graff Zivin, D. Hershman, A.I. Neugut, V.R. Grann.

Final approval of the article: K. Anderson, J.S. Jacobson, D.F. Heitjan, J. Graff Zivin, D. Hershman, A.I. Neugut, V.R. Grann.

Provision of study materials or patients: K. Anderson, V.R. Grann.

Statistical expertise: K. Anderson, D.F. Heitjan, V.R. Grann.

Obtaining of funding: K. Anderson, V.R. Grann.

Administrative, technical, or logistic support: K. Anderson, V.R. Grann.

Collection and assembly of data: K. Anderson.