Abstract

Polygenic risk scores (PRS) offer a novel means of stratifying breast cancer risk, with the potential to personalize screening protocols and measures, and thus improve early detection. However, their implementation in real-world settings remains poorly understood. This study, as part of the BRIGHT project, investigates how PRS-based breast cancer screening is being piloted, adapted, and resisted across five European countries, Estonia, Portugal, Spain, Sweden, and France, drawing on a combination of implementation science and business model theory. We employed a multiple-case study approach, conducting 94 semi-structured interviews with stakeholders across healthcare, policy, industry, and civil society. Analysis was guided by the Value–Information–Process (VIP) framework and complemented by selected constructs from the Consolidated Framework for Implementation Research (CFIR). Data were coded thematically and triangulated with national policy documents, pilot evaluations, and stakeholder workshops. Implementation trajectories varied significantly across contexts. Estonia demonstrated advanced policy-driven integration enabled by digital infrastructure and centralized governance. Sweden and Spain followed pilot-to-policy models, with strong regional autonomy but slower national uptake. Portugal exhibited market-led adoption driven by private sector innovation, while France pursued a trial-first logic centered on MyPeBS. Common barriers included limited clinical guidelines, low genetic literacy among frontline providers, fragmented IT systems, and slow and unclear Health Technology Assessment (HTA) cycles. Key facilitators included strong institutional alignment, biobank-linked infrastructures, and public trust in preventive care. Successful PRS implementation requires more than scientific validation; it depends on systemic readiness across value narratives, information systems, and governance processes. PRS-based screening thus serves as a test case for the broader challenge of integrating personalized genomics into public health. Findings offer strategic guidance for policymakers, clinicians, and researchers designing future-ready prevention pathways.