ABSTRACT
Background: Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach. Methods: MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants. Results: As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer;72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality;and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks). Conclusions: Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants. Clinical trial identification: NCT03672331. Legal entity responsible for the study: Unicancer. Funding: European Commission and French National Cancer Institute. Disclosure: S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Exact Sciences;Financial Interests, Institutional, Advisory Board: Novartis;Financial Interests, Institutional, Advisory Board: Pierre fabre;Financial Interests, Institutional, Advisory Board: Orion;Financial Interests, Institutional, Advisory Board: Sanofi;Financial Interests, Institutional, Advisory Board: Rappta;Financial Interests, Institutional, Advisory Board: Cellectis;Financial Interests, Institutional, Advisory Board: Isis/servier;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker: Seagen;Financial Interests, Institutional, Invited Speaker: Lilly;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: MSD;Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare;Financial Interests, Institutional, Invited Speaker: Roche Genentech;Financial Interests, Institutional, Invited Speaker: BMS;Financial Interests, Institutional, Invited Speaker: Puma;Financial Interests, Institutional, Invited Speaker: AstraZeneca;Financial Interests, Institutional, Invited Speaker: Orion;Financial Interests, Institutional, Invited Speaker: Sanofi;Financial Interests, Institutional, Funding: GE;Financial Interests, Institutional, Invited Speaker: Pfizer;Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho;Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife;Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI;Financial Interests, Personal, Advisory Role: Amaris;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Sensorion;Financial Interests, Personal, Advisory Role: Biophytis;Financial Interests, Personal, Advisory Role: Servier;Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.