Abstract OT2-10-02: Mypebs: An international randomized study comparing personalized, risk-stratified to standard breast cancer screening in women aged 40-70

Abstract Background Currently, mammographic-based breast cancer screening (BCS) using age as the single criterion for population selection, apart from rare high-risk indications, is being questioned for its imperfect sensitivity (interval cancers) and specificity (false positive recalls), as well as the risk of over-diagnoses. BC risk scores incorporating personal and family history, breast mammographic density and genetic information based on a polygenic score (PRS) give a promisingly accurate likelihood of a woman developing invasive BC in the next 5 years. MyPeBS, a European Commission H2020-funded randomized clinical trial (NCT03672331) conducted in 6 countries (Belgium, France, Israel, Italy, Spain and UK) aims to demonstrate the usefulness of a risk-based screening approach to improve BCS in the general population. Methods MyPeBS’s primary objective is to show non-inferiority of the risk-stratified BCS arm in terms of incidence rate of breast cancer of stage 2 and higher, compared to the standard BCS arm. The key secondary objective, if non-inferiority is shown, is to demonstrate superiority of the risk-based screening arm. MyPeBS also assesses whether this strategy allows reduces morbidity (less false positives); is equally or more cost-effective, and impacts women’s understanding, awareness and emotional responses as compared to standard of care. Women aged 40 to 70 are eligible if they did not have prior BC or high risk-condition, and live in a participating country and area. Participants are randomized 1:1 between standard BCS according to country’s/region’s ongoing policy, or risk-stratified BCS, where screening frequency and method depend on their individual 5 year predicted risk of invasive BC (Table 1). Stratification factors include age, prior mammogram and country. Risk assessment uses a centralized genotyping on a saliva sample to assess PRS 313 (Mavaddat et al, Am J Hum Genet 2019), which is embedded in either a BCSC-derived score for women with at most one first-degree relative with BC; or Tyrer-Cuzick score for women with > 1 family member with breast cancer. Women participate for 4 years. Planned accrual is 85000. On June 30th, 2021, 13882 women have been randomized. Table 1.BC Screening schedule in MyPeBS’ Risk-based armRisk levelLow riskAverage riskHigh riskVery high riskNumerical definition (invasive breast cancer risk at 5 years)<1%1-1.66%≥ 1.66% and < 6%≥ 6%Mammogram1 at end of study (4 years)Every 2 yearsYearlyYearlyAdditionalYearly breast cancer awareness reminderHigh density: US or ABUS every 2 yearsHigh density: US or ABUS every 2 yearsAnnual MRI until age 60 Citation Format: Suzette Delaloge, Paolo Giorgi Rossi, Michal Guindy, Fiona Gilbert, Jean-Benoit Burrion, Corinne Balleyguier, Marta Roman Exposito, Livia Giordano, Harry De Koning, Sandrine de Montgolfier, Stephane Ragusa, Damien Drubay, Marie-Eve Rouge-Bugat, Gareth D Evans, Debbie Keatley, Helene Blanche, Anne Boland, Emilien Gauthier, Aloys Dubois d'Aische, Cécile Vissac-Sabatier, Daniel Couch, Camille Baron, Jean-François Deleuze, Paul Pharoah, Stefan Michiels. Mypebs: An international randomized study comparing personalized, risk-stratified to standard breast cancer screening in women aged 40-70 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-10-02.