Cost-effectiveness of genetic testing for BRCA1 and BRCA2 mutations.
Authors: Ozanne EM , Cipriano L , Cameron M , Newman T , Esserman LJ 
Published: December 2010

Abstract
Abstract #6100
Purpose&#x2028; Women who carry a BRCA1 or BRCA2 genetic mutation are at significantly increased risk of breast and ovarian cancer. Current guidelines recommend genetic testing of women who have a greater than 10% likelihood of carrying a mutation. We sought to evaluate the cost-effectiveness of this suggested guideline by simulating genetic testing in cohorts of women at various risk for the BRCA1 and BRCA2 genetic mutations.&#x2028; Methods&#x2028; A Markov model was developed to compare the effectiveness and cost-effectiveness of genetic testing in cohorts of 30-year old women without a prior breast or ovarian cancer diagnosis at varying likelihoods of carrying a genetic mutation. Women who test positive for a mutation were assumed to select surgical prevention (mastectomy, oophorectomy, or both mastectomy and oophorectomy) at previously observed rates in carrier populations. Costs were estimated using Medicare reimbursement rates and secondary sources. Transition rates and other model variables were estimated from the literature. Effectiveness was measured in life-years gained and quality-adjusted life-years (QALYs) gained.&#x2028; Results&#x2028; In a high-risk cohort of women aged 30 of whom 10% are expected to carry a BRCA mutation, genetic testing has an incremental cost-effectiveness ratio (ICER) of less than $50,000 per life-year gained and of less than $50,000 per QALY gained in most scenarios. The proportion of women carrying a genetic mutation did not significantly affect this result. However, among women who are not eligible for intensive surveillance (mammography, transvaginal ultrasound, annual CA-125 blood test) at age 30, the incremental cost per QALY gained increases to greater than $50,000. Very low rates of prophylactic surgery in mutation carriers can cause genetic testing to become prohibitively expensive. Genetic testing is also prohibitively expensive if testing identifies a large number of individuals with variant of unknown significance (VUS) or uninformative negative results, especially if those individuals have moderate or high rates of prophylactic intervention.&#x2028; Conclusions&#x2028; Current guidelines for genetic testing are cost effective under most scenarios considered; however, these results are dependent on a number of variables. Surprisingly, these results are less dependent on the proportion of mutation carriers in the testing cohort than the proportion of women who are found to have VUS or uninformative negative results and the rate of prophylactic intervention in that population, as the value of these interventions is lower in this group. Cost-savings generated by decreased surveillance in the population that tests negative greatly influences the cost effectiveness of genetic testing, a result that will be strengthened as MRI becomes more widespread in the high-risk population. These results suggest that genetic testing is cost-effective in any population that is at significant risk to warrant intensive surveillance.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6100.