Cost-effectiveness of surgical interventions for BRCA gene mutation carriers: impact of delaying decision-making.

Abstract

Abstract Abstract #503 Purpose
 Women who carry a BRCA1 or BRCA2 genetic mutation are at significantly increased risk of breast and ovarian cancer. Interventions to reduce the risk of these cancers available these women include bilateral prophylactic mastectomy (PM) and oophorectomy (PO), or both (PMPO). However, women are often reluctant to choose these options, and prefer to delay these surgeries for childbearing or other reasons. We sought to identify the effectiveness and cost-effectiveness of these interventions and to evaluate the potential consequences of delaying prophylactic surgery in terms of risk of cancer diagnosis and life expectancy.
 Methods
 A Markov model was developed to compare the effectiveness and cost-effectiveness of prophylactic surgery in cohorts of women with the BRCA1 and BRCA2 mutations without prior breast or ovarian cancer. Multiple strategies were explored to evaluate the benefit of these interventions at various ages. Costs were estimated using Medicare reimbursement rates and secondary sources. Other model variables were estimated from the literature. Effectiveness was measured in life-years gained and quality-adjusted life-years gained in addition to breast and ovarian cancers diagnosed.
 Results
 All surgeries significantly prolong survival at all ages explored (age 30 to 45), although much more so in younger women and in BRCA1 compared to BRCA2 carriers. BRCA1 carriers at age 30 have an increased life expectancy of 4, 8, and 13 years for PM, PO, and PMPO, whereas BRCA2 carriers have an increased life expectancy of 3, 3, and 6 years respectively, vs. 2, 4, 6 years (BRCA1) and 2, 2, 4 years (BRCA2) at age 45. BRCA1 carriers who delay prophylactic surgery are projected to have a 6.4% chance of a cancer diagnosis before age 35 vs. 35% chance before age 45. BRCA2 carriers who delay surgery are projected to have a 2.6% vs. 12.1% chance of cancer diagnosis before age 35 and 45 respectively. Compared to surveillance, all options have incremental cost effectiveness ratios (ICER) less than $50,000 per quality adjusted life year gained in BRCA1 carries. However, some of these strategies are not considered cost-effective in BRCA2 carriers.
 Conclusions
 Surgical prophylactic interventions for known BRCA mutation carriers are very effective and cost-effective, although more so in younger women and in BRCA1 carriers as compared to BRCA2 carriers. These interventions are life-saving even when delayed; however, for individuals who have high disutility for prophylactic surgery, these options may reduce quality-adjusted life expectancy regardless of when the surgery is performed. Patients need to be aware of the short-term cancer risk from delaying prophylactic intervention to ensure informed trade-offs. Selection of individuals who perceive low harm or anticipate minimal adjustment to the prophylactic interventions will ensure cost-effective use of these surgical interventions. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 503.