PRS-Based Breast Cancer Screening: a GRADE Framework for Why Europe Should Pilot Before Adopting

Breast cancer screening programmes apply uniform protocols that do not account for individual risk variation. Polygenic risk scores (PRSs), aggregating effects of cancer-associated variants, could enable risk-stratified screening tailored to individual profiles. However, whether PRS integration improves outcomes sufficiently to justify implementation in European health systems remains uncertain. We developed recommendations using the GRADE Evidence-to-Decision (EtD) framework. Within the CanHeal EU funded initiative, a multidisciplinary panel evaluated evidence across EtD domains: benefits and harms, acceptability, feasibility, cost-effectiveness, and equity. Judgements were informed by a systematic review of decision-analytic models and two reviews on implementation aspects. Panel consensus was elicited through two structured rounds. Results from the WISDOM pragmatic trial, published after voting, were incorporated as complementary narrative evidence. The panel judged the benefit-harm balance as highly uncertain, with modest projected gains in life-years and QALYs, partially offset by increased false positives and overdiagnosis. Acceptability was rated moderate, supported by WISDOM data; feasibility as context-dependent and constrained by infrastructure gaps and limited workforce readiness. Equity concerns were rated as substantial, given reduced PRS predictive performance in non-European populations. Cost-effectiveness was plausible but insufficiently validated for routine policy decisions. These are the first European, GRADE EtD-based recommendations on PRS integration in breast cancer screening. Given very low certainty and context-dependent trade-offs, the panel conditionally recommends against routine adoption. National and regional health systems should instead support pragmatic, setting-specific implementation pilots with explicit equity safeguards, outcome monitoring, and iterative evaluation to generate the evidence needed for future policy decisions.

Key messages

• A European expert panel, applying the GRADE EtD framework, conditionally recommends against routine PRS adoption in breast cancer screening, citing very low certainty and context-dependent trade-offs.

• Very low certainty of evidence and equity concerns led the panel to recommend piloting over adoption, prioritising learning systems with real-time monitoring across diverse populations.