Defining Lifetime Risk Thresholds For Breast Cancer Surgical Prevention: A Cost-Effectiveness Analysis

Abstract

Introduction/Background Improvement in cancer risk prediction and falling costs of genetic testing are increasingly identifying women at elevated risk of breast cancer (BC) who are not BRCA1/BRCA2/PALB2 carriers. These women may wish to access risk-reducing mastectomy (RRM). This study aims to define the lifetime BC-risk thresholds for RRM to be cost-effective compared with non-surgical alternatives for BC prevention. Methodology A decision-analytic Markov model compared the cost-effectiveness of RRM with BC screening and medical prevention, among women aged 30-60 years at varying lifetime BC-risks from 17%-50%. The analysis was conducted from UK health-system payer perspective with a lifetime horizon. Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. Results For 30-year-old women, undergoing RRM became cost-effective for a 34% lifetime BC-risk with an ICER of 28,861/QALY, using 30,000/QALY WTP-threshold, which increased to a 42% lifetime BC-risk with an ICER of 19,553/QALY, using 20,000/QALY WTP-threshold. The identified lifetime BC-risk thresholds for RRM to be cost-effective among 35-, 40-, 45-, 50-, 55-, and 60-year-old women were 31%, 29%, 29%, 32%, 36%, and 42%, respectively, using 30,000/QALY WTP-threshold. Overall, undergoing RRM at ages 30-55 was deemed cost-effective for women with a >=35% lifetime risk, with >50% simulations being cost-effective in probabilistic-sensitivity-analysis (PSA). Offering RRM could potentially prevent ~6500 BC cases annually for women with a lifetime BC-risk >=35% in the UK. The risk threshold increased to 41% for a longer (2-year) disutility from surgery. In the PSA, 55.04%, 87.36%, and 99.35% simulations were cost-effective for women with 34%, 42%, and 50% lifetime BC-risk undergoing RRM at age 30. Conclusion Undergoing RRM at ages 30-55 appears cost-effective for women with a >=35% lifetime BC-risk. The results could have significant clinical implications to expand access to RRM beyond BRCA1/BRCA2/PALB2 carriers. Future studies on understanding the acceptability, uptake, and long-term impact of RRM among these women are warranted.