MyPeBS addresses the crucial and timely question of the future of breast cancer screening in Europe. Indeed current standard mammographic screening, with entry stratified by age alone, has recently been largely questioned. Despite a demonstrated mean 20% reduction in breast cancer-specific mortality, together with reduction of late-stage disease in women older than 50, it is associated with potential harms including false positive recalls and over-diagnosis. Individual breast cancer risk estimation, through models including clinical variables, mammographic breast density and more than 100 genetic polymorphisms, now has substantial clinical and scientific bases. Personalized screening strategies, based on individual risk levels, could potentially improve the individual benefit/harms ratio of screening (earlier cancer detection and less intensive treatments in high risk women, less false positives and over-diagnoses in low risk ones), and increase the cost-efficacy for health insurances. MyPEBS will conduct an international randomized phase III trial to validate this hypothesis. It will primarily assess the ability of an individual risk-based screening strategy to be non-inferior, and possibly superior, to the standard of care screening, in reducing the cumulative incidence of stage II+ breast cancers. The trial, conducted in 5 countries (France, Italy, UK, Belgium and Israel) will include 85000 European women aged 40-70, all followed for 4 years. MyPEBS will also evaluate if an individual risk-based screening strategy, compared with the standard, reduces screening-related harms (unnecessary biopsies, overdiagnoses) in low-risk women, is overall at least as cost-effective as well as more accepted by women resulting in a larger screening coverage. After analyses of all components, the final objective of MyPEBS is to deliver recommendations for the best future breast cancer screening strategy in Europe.