COST-EFFECTIVENESS OF POLYGENIC RISK-GUIDED BREAST CANCER SCREENING WITH AND WITHOUT HBOC TESTING: A DISCRETE-EVENT SIMULATION WITH PROBABILISTIC SENSITIVITY ANALYSIS
Author(s)
Greg Guzauskas, MSPH, PhD1, Shawn Garbett, MS2, Jinyi Zhu, PhD3, John Graves, PhD2, Jiayu Shi, MS2, Marc S. Williams, MD4, Jing Hao, MPH, MS, PhD, MD5, Josh Peterson, MD2, David Veenstra, PharmD, PhD6;
1The CHOICE Institute, Senior Research Scientist, Orcas, WA, USA, 2Vanderbilt University, Nashville, TN, USA, 3Vanderbilt University Medical Center, Nashville, TN, USA, 4Geisinger Health, Danville, PA, USA, 5Geisinger Health System, Danville, PA, USA, 6CHOICE Institute, University of Washington, Seattle, WA, USA
1The CHOICE Institute, Senior Research Scientist, Orcas, WA, USA, 2Vanderbilt University, Nashville, TN, USA, 3Vanderbilt University Medical Center, Nashville, TN, USA, 4Geisinger Health, Danville, PA, USA, 5Geisinger Health System, Danville, PA, USA, 6CHOICE Institute, University of Washington, Seattle, WA, USA
OBJECTIVES: To evaluate the cost-effectiveness of population-based polygenic risk score (PRS) testing for breast cancer, alone and in combination with hereditary breast and ovarian cancer (HBOC) testing, accounting for age at testing, intensified screening among high-risk women, and preventive surgery uptake.
METHODS: We developed a lifetime discrete-event simulation model of U.S. women undergoing no testing, PRS-guided screening at high-risk percentile thresholds (≥80%, ≥90%, ≥95%), HBOC testing alone, or combined PRS+HBOC strategies. High-risk women received earlier and more frequent mammography and magnetic resonance imaging (MRI) screening. Ten thousand simulated women were seeded with entry age, PRS percentile, HBOC status, and preventive surgeries among HBOC carriers, and followed for breast and ovarian cancer incidence, stage at diagnosis, and cancer-specific and all-cause mortality. Cancer risks were calibrated to SEER incidence with PRS-specific relative risks. Costs and utilities were derived from scientific literature. Probabilistic sensitivity analyses (2,500 simulations per strategy) were conducted for testing ages 20, 30, 40, and 50 years.
RESULTS: PRS-only strategies generated small incremental QALYs (<0.006) versus no testing. Higher PRS thresholds reduced screening costs but also limited the number of women benefiting from intensified screening. PRS-only incremental cost-effectiveness ratios (ICERs) ranged from approximately $1.6 million to $11 million versus no testing, largely driven by increased screening costs. HBOC-only testing was consistently the most cost-effective strategy and was cost-saving relative to no testing at ages 30 and 40, driven by avoided cancer treatment costs following preventive surgery; at age 20, the ICER was $5,200 versus no testing. Combined PRS+HBOC strategies had the highest absolute QALY gains but were less cost-effective overall, with ICERs ranging from $120,400 to $859,100.
CONCLUSIONS: HBOC testing alone is the most cost-effective genetic testing strategy across testing ages. PRS-guided screening provides marginal population-level health gains at substantially higher cost, even when restricted to higher-risk thresholds.
METHODS: We developed a lifetime discrete-event simulation model of U.S. women undergoing no testing, PRS-guided screening at high-risk percentile thresholds (≥80%, ≥90%, ≥95%), HBOC testing alone, or combined PRS+HBOC strategies. High-risk women received earlier and more frequent mammography and magnetic resonance imaging (MRI) screening. Ten thousand simulated women were seeded with entry age, PRS percentile, HBOC status, and preventive surgeries among HBOC carriers, and followed for breast and ovarian cancer incidence, stage at diagnosis, and cancer-specific and all-cause mortality. Cancer risks were calibrated to SEER incidence with PRS-specific relative risks. Costs and utilities were derived from scientific literature. Probabilistic sensitivity analyses (2,500 simulations per strategy) were conducted for testing ages 20, 30, 40, and 50 years.
RESULTS: PRS-only strategies generated small incremental QALYs (<0.006) versus no testing. Higher PRS thresholds reduced screening costs but also limited the number of women benefiting from intensified screening. PRS-only incremental cost-effectiveness ratios (ICERs) ranged from approximately $1.6 million to $11 million versus no testing, largely driven by increased screening costs. HBOC-only testing was consistently the most cost-effective strategy and was cost-saving relative to no testing at ages 30 and 40, driven by avoided cancer treatment costs following preventive surgery; at age 20, the ICER was $5,200 versus no testing. Combined PRS+HBOC strategies had the highest absolute QALY gains but were less cost-effective overall, with ICERs ranging from $120,400 to $859,100.
CONCLUSIONS: HBOC testing alone is the most cost-effective genetic testing strategy across testing ages. PRS-guided screening provides marginal population-level health gains at substantially higher cost, even when restricted to higher-risk thresholds.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EE44
Topic
Economic Evaluation
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology, STA: Genetic, Regenerative & Curative Therapies, STA: Personalized & Precision Medicine