Abstract P4-09-03: Simulated outcomes of personalized versus guideline-based breast cancer screening
Authors: Shieh Y , Esserman L , Eklund M 
Published: May 2019

Abstract
Introduction: Personalized screening, or screening tailored to individual breast cancer risk, is being studied as an improvement on the current practice of guideline-based screening. WISDOM (Women Informed to Screen Depending on Measures of Risk) is an ongoing randomized trial comparing personalized to annual screening. To project the efficacy, safety, and cost of personalized screening on a population level, we constructed a simulation model comparing personalized to guideline-based strategies across the outcomes of advanced (Stage IIB+) cancers, false positives, biopsies, and cost.
Methods: Our simulated cohort consisted of 100,000 women aged 40-74 with demographic and risk factor distributions based on the U.S. screening population. We modeled the WISDOM approach to personalized screening where recommendations are based on the results of panel-based mutation testing and 5-year risk estimates from a clinical risk model modified by a polygenic risk score containing 76 genetic variants (SNPs). Simulated women were randomly assigned a clinical and genetic risk profile, which were integrated to generate a 5-year risk estimate. This was then used to assign a starting and stopping age, frequency, and modality (MRI vs. mammogram) of screening. We compared the aggregate outcomes over a 1-year time window between personalized screening and 3 strategies based on U.S. professional society guidelines (Table).
Results: There was no statistically significant difference in advanced cancers between screening strategies (Table). However, the biennial, hybrid, and personalized strategies resulted in fewer false positives and biopsies compared to annual screening, and at lower cost. Though aggregate outcomes between the hybrid and personalized strategies were similar, the average 5-year risk of women assigned to annual screening under the personalized strategy was higher than that of the hybrid strategy, 1.7% vs. 1.2%. Similarly, the average 5-year risk of women assigned to biennial screening was lower under the personalized strategy, 1.1% vs. 1.9%.
Conclusion: Our simulations show that personalized screening results in a similar incidence of advanced cancers as annual screening while reducing false positives, biopsies, and cost. Compared to other guideline-based strategies, personalized screening better allocates screening resources by identifying higher-risk women for more intensive screening, and lower-risk women for less intensive screening.
Descriptions and simulated outcomes of four screening strategiesStrategyStarting age, yearsStopping age, yearsFrequencyStage IIB+ cancers, RR1 (95% CI)2False positives, RR1 (95% CI)2Biopsies, RR1 (95% CI)2Cost, millions USD per 100,000 womenAnnual (American College of Obstetricians and Gynecologists)4074Annualrefrefref$22.1Biennial (U.S. Preventive Services Task Force)5074Biennial1.13 (0.98-1.28)0.44 (0.33-0.56)0.46 (0.35-0.58)$8.4Hybrid (American Cancer Society)45Per life expectancy45-55: Annual 55+: Biennial1.09 (0.95-1.25)0.58 (0.49-0.67)0.64 (0.56-0.73)$14.7Personalized (WISDOM)40-503Per life expectancyAnnual or Biennial41.01 (0.89-1.12)0.55 (0.46-0.65)0.56 (0.47-0.65)$14.11relative risk; 295% confidence interval; 3start when 5-year risk &gt; 1.3%; 4annual if age 40-49 + dense breasts or top 2.5th percentile of 5-year risk
Citation Format: Shieh Y, Esserman L, Eklund M. Simulated outcomes of personalized versus guideline-based breast cancer screening [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-09-03.