Modeling a Histology-Based Referral System to Reduce Breast and Ovarian Cancer in BRCA1/2 Carriers [240

Abstract

OBJECTIVE: Despite recent advances in histopathology and genetics of inherited breast and ovarian cancer, many asymptomatic BRCA1/2 carriers remain undetected. We describe a histology-based referral model of genetic counseling and testing of patients with “high-risk” breast and ovarian cancer to identify asymptomatic BRCA1/2 carriers and evaluate the cost-effectiveness of cancer prevention strategies. METHODS: The model utilizes breast and ovarian cancer registry data to estimate the number of asymptomatic BRCA1/2 carriers that would be identified based on assumptions derived from the literature. Furthermore, patient-specific life expectancy, prevention strategy effectiveness, age-related cancer probabilities, health outcomes, and cost-effectiveness of the different prevention options were evaluated. RESULTS: Using Kentucky Cancer Registry breast and ovarian cancer pathology data for the decade 2001–2010, 2,708 asymptomatic BRCA1/2 carriers were identified at a cost of approximately $9,000 per carrier. Risk-reducing surgery was the most successful prevention strategy, preventing 2,220 breast and ovarian cancers at a cost of $81,595 per cancer avoided. “Chemoprevention” prevents 637 breast and ovarian cancers at a cost of $677,000 per cancer avoided. “Surveillance” does not reduce cancer incidence. CONCLUSION: A histology-based referral system has the potential to identify asymptomatic BRCA1/2 carriers. Model yield of asymptomatic carriers would be improved with more sophisticated breast cancer inclusion criterion (receptor status, histology, age, and grade). Asymptomatic carrier counseling should be mutation-specific. Risk-reducing surgery is the most cost-effective prevention strategy for both mutations. The most costly strategy is surveillance with no reduction in breast and ovarian cancer incidence.