Abstract PS3-01-12: Wisdom and mypebs: personalized breast cancer screening trials operating in distinct international contexts

Abstract Background WISDOM (Women Informed to Screen Depending on Measures of risk) (NCT02620852) and MyPeBS (My Personal Breast Screening) (NCT03672331) are two prominent risk-based breast cancer screening (RBS) trials based in the US and Europe & Israel, respectively. Both trials aim to assess whether RBS is as safe as current screening (no increase incidence of stage> II/IIB breast cancers) and can aid to enhance resources on those at higher risk, while minimizing harm to those at lowest risk. WISDOM and MyPeBS were conducted independently but with a planned joint analysis. Guidelines in the US range from annual (ACR, NCCN) to biennial screening starting at age 40 (USPSTF). In contrast, screening in MyPeBS countries is population-based by invitation every 2 years in (France, Belgium, Italy, Spain, Israel) and every 3 years in the UK starting at age 50. We will compare the baseline characteristics of both cohorts. Methods Eligibility included ages 40-74 in WISDOM and 40-70 in MyPeBS and no prior breast cancer history. Both are randomized 1:1 to RBS vs. country-based standard of care screening, though in WISDOM, women could choose their arm if they declined randomization (pragmatic, preference tolerant approach). Methods of recruitment reflect systematic/screening invitation (EU) vs. opportunistic (US). In WISDOM, the 5-year risk of invasive BC is estimated using the Breast Cancer Screening Consortium (BCSC) score, which includes clinical data & breast density, combined with a Polygenic Risk Score (PRS) (up to 126 single nucleotide polymorphisms (SNPs)), & a panel to identify germline mutations in 9 breast cancer risk genes. Four categories were used to classify risk (lowest, average, elevated, & highest), with corresponding screening assignments: age-based (mammogram (Mg) starting at 50), two-year (average), one-year moderate risk (MR), or Q6 (alternating Mg and MRI every 6 months). MR/Q6 includes breast health specialist consultation to discuss risk reduction and the Breast Health Decisions tool (automated risk/prevention recommendations, which is available to all patients). In MyPeBS, the 5-year risk is estimated using the Mammorisk™/BCSC model + PRS 313, or Tyrer-Cuzick (TC) + PRS 313 among women who have >1 first-degree family history of breast cancer (FDFH) with BC. Absolute risk cutoffs are defined as ‘low’ (<1%), ‘average’ (1–1.66%), ‘high’ (>1.66–6%), and ‘very high’ (≥6%) with corresponding screening assignments: next Mg at 4 years, Mg every 2 years, annually, or annually + MRI. Results WISDOM and MyPeBS enrollment was 46,289 and 53,143 women, respectively. Using the MyPeBS absolute risk cutoffs, the risk distribution for WISDOM and MyPeBS respectively were similar: ‘very high,’ (1% vs. 2%); ‘high’ (31% vs 33%), ‘average’ (26% vs 29%) & ‘low’ (40% vs 37%). Between the two trials, the screening recommendations for the low-risk group were the most different: every 2 years starting at 50 in WISDOM vs. next Mg at 4 years in MyPeBS. Median age was similar (54 vs. 55), though the percentage of women in their 40s was higher in WISDOM (38% to 23%). Baseline BMI was higher in WISDOM (27.6 vs 25.3). Differences (WISDOM vs MyPeBS) include: Education levels, with college degrees in 76% vs 52%; rates of prior biopsies 24% vs 14%; presence of a first-degree family member 24% vs 17%; and the use of hormonal replacement in the postmenopausal women 45% vs 17%. Chemoprevention use at baseline in both trials was 1% or less. Conclusion Within these two major trials, thresholds for risk assignment and proportion of patients in the personalized risk groups are very similar as are screening schemes except for low-risk women (every 2 yrs (WISDOM) vs. every 4 yrs (MyPeBS)). Variation provides the opportunity to learn from the effect of different practice patterns. Data emerging from both trials should be generalizable and have the potential to be practice-changing. Citation Format: K. Leggat-Barr, P. Giorgi Rossi, M. Guindy, F. Gilbert, M. Roman, J. Burrion, H. De Koning, S. de Montgolfier, L. Giordano, D. Keatley, J. Deleuze, E. Gauthier, S. Michiels, C. Vissac-Sabatier, H. Anton-Culver, S. Borowsky, S. Brain, J. Esserman, E. Ziv, A. Fiscalini, D. Goodman-Gruen, D. Heditsian, R. Hiatt, V. Lee, D. Moorehead, A. Naiem, O. Olopade, H. Park, B. Parker, A. Petruse, M. Scheuner, L. van ‘t Veer, V. Arasu, M. Eklund, L. Madlensky, Y. Shieh, N. Wenger, J. Tice, C. Kaplan, A. Kaster, R. Lancaster, A. LaCroix, S. Delaloge, L. Esserman. Wisdom and mypebs: personalized breast cancer screening trials operating in distinct international contexts [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-12.