Real-time genotyping-based breast cancer risk assessment in MyPeBS, an international randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS)

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 11 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.