Genetic counseling and subsequent cascade genetic testing for women with a family history of pathogenic BRCA1 mutation: A cost-effectiveness model.

Abstract

10621 Background: BRCA1 pathogenic mutations significantly increase the lifetime risk for breast and ovarian cancer, but risk reducing interventions such as bilateral salpingo-oophorectomy (RRBSO) and mastectomy (RRM) can improve outcomes. For women with a known family history of pathogenetic mutation, genetic counseling and testing is recommended. We sought to determine the cost-effectiveness (CE) of referral to genetic counseling with subsequent cascade testing. Methods: A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine genetics consultation with Ambry panel testing versus no referral. It was assumed that known BRCA1 carriers would undergo annual breast cancer screening with mammogram and MRI at 25yo, RRBSO at 35yo, and RRM at 40yo. Non-carriers underwent routine annual mammogram at 40yo. Additionally, women who did not undergo genetic testing initially do so at the time of diagnosis of first cancer (breast of ovary) and subsequently underwent all recommended risk reducing strategies if found to have a pathogenic BRCA1 mutation. Outcomes included cost, quality adjusted life years (QALYs), ovarian and breast cancer cases and deaths. Univariate and multi-variate analyses were used to investigate the impact of the strategies. Results: In a Monte Carlo Microsimulation cohort of 10,000 women with a first degree relative with a pathogenic BRCA1 mutation, referral to genetic counseling with testing was the dominate strategy. This strategy resulted in a similar mean cost ($185,543 vs $185,171), but with 2,322 additional QALYs and incremental CE ratio (ICER) of 1,605 per QALY. This dominant strategy also resulted in 73 fewer ovarian cancer cases and 545 fewer breast cancer cases. Sensitivity analysis for the age of RRM was remarkable for an annual reduction in breast cancer cases by 97 cases and an annual cost savings of 375,658 for year prior to age 40 that mastectomy was performed. Conclusions: Routine genetic counseling and screening for all patients with a known family history of pathogenic BRCA1 mutation reduces breast and ovarian cancer diagnoses by prompting risk-reducing procedures without significant increase in cost when compared to diagnosis-based testing. Routine access to genetic counseling in a high-risk population would help inform earlier counseling and further decrease cancer risk, particularly as earlier RRM may improve outcomes. This is further supported by the low cost to implement. Improvement in identification and early referral could be targeted. [Table: see text]