Integrating Genetic Risk Models in Breast Cancer Prevention: A Pilot Study

Abstract Breast cancer remains the most common malignancy among women, significantly impacting public health. Despite advancements in early diagnosis and treatment, identifying risk factors and developing personalized prevention strategies are crucial. The polygenic risk scores (PRS), combined with other risk factors as in the CanRisk model, have the potential to improve risk stratification and breast cancer prevention. This study evaluates the feasibility of implementing the CanRisk model incorporating PRS for breast cancer prevention, as part of the clinical pathway of the Medical Genetics Clinic at Fondazione Policlinico Universitario Agostino Gemelli in Italy. This single-arm pre-post interventional study, conducted over 12 months, enrolles 200 healthy women with a family history of breast cancer or known pathogenic variants. Women undergo CanRisk assessment, including PRS testing and genetic counseling. The study evaluated whether the addition of PRS modifies the CanRisk score and assessed women acceptance and perceptions of the clinical pathway through a validated questionnair. In a preliminary analysis on 85 women, 70 (82%) accepted the CanRisk assessment with PRS testing, that modified the risk score in 10 participants (15%). Regarding perceptions, 62 participants (89%) reported that the suggested pathway allocates enough time to explicating PRS and results, but only 15/70 (21%) were concerned that their General Practitioners were not aware about the existence of PRS and its role in breast cancer prevention. The preliminary results suggest that incorporating PRS into the CanRisk model is feasible and well-received in a clinical setting, significantly improving risk stratification and potentially improving patient engagement in preventive strategies. These results support the potential for broader implementation of integrated genetic risk models in personalized breast cancer prevention. This work is part of the DARE - Digital Lifelong Prevention Project, B53C22006320001. Key messages • Incorporating polygenic risk scores (PRS) into the CanRisk model for breast cancer prevention is feasible and well-received in a clinical setting. • The addition of PRS to the CanRisk model significantly improves risk stratification.