This single-arm interventional feasibility study will evaluate whether integrating polygenic risk scores (PRS) into the CanRisk model can improve breast cancer risk prediction and personalized prevention in women at risk of breast cancer. The study will assess the organizational feasibility, patient acceptance, emotional impact and satisfaction of an integrated pathway combining PRS testing with standard genetic counseling and other risk factors at Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
Ability to provide informed consent
Voluntary consent to participate
Estimated risk of carrying an inherited pathogenic variant (in BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1) > 5%, (calculated on www.canrisk.org)
Known family history of breast cancer, or
Diagnosis or history of bilateral breast cancer
Diagnosis of ductal carcinoma in situ
Previous bilateral mastectomy
Life expectancy < 12 months due to other medical conditions
Single group
Clinical pathway for breast cancer prevention based on PRS-integrated CanRisk assessment
GeneticStandard genetic counseling followed by a blood draw (0.5 mL) for DNA extraction. The sample is processed using a high-throughput SNP genotyping platform, and the PRS, based on 313 SNPs, is calculated and integrated into the CanRisk model for refined breast cancer risk stratification. In conjunction with result disclosure, participants complete structured questionnaires to assess psychological impact and risk comprehension (questionnaire by Woof et al.). At the end of the study, both participants and healthcare professionals complete feasibility questionnaires to evaluate the implementation of the PRS-integrated clinical pathway (Care Process Self-Evaluation Tool, CPSET; Vanhaecht et al.).
Feasibility of implementing an integrated clinical pathway including PRS
The primary outcome is the feasibility of integrating polygenic risk score (PRS) testing into the CanRisk breast cancer risk model within a structured clinical pathway. Feasibility will be assessed using the Care Process Self-Evaluation Tool (CPSET), that includes 27 items across 5 domains: patient-centeredness, coordination of care, communication, cooperation, and monitoring/follow-up. The questionnaire will be administered at the end of the study to both enrolled women and involved healthcare professionals.
Uptake of CanRisk+PRS integrated pathway
Proportion of women accepting PRS testing among those offered: (Number accepting PRS / Number offered PRS) × 100
Proportion of women requesting their individual CanRisk+PRS result
The percentage of enrolled women who actively request to receive their individualized breast cancer risk estimate generated by the CanRisk model integrated with PRS. This outcome will measure the degree of patient interest in receiving personalized genomic risk information.
Percentage of women reclassified into different risk categories after PRS integration
The percentage of women whose risk category (low, moderate, or high) changes when PRS information is added to their baseline CanRisk estimate. This outcome will assess the clinical utility of PRS in refining breast cancer risk stratification and identifying women who may benefit from adjusted preventive strategies.
Proportion of women with modified prevention pathways after PRS-informed reclassification
The percentage of women whose preventive or follow-up pathway is modified following a multidisciplinary team review prompted by PRS-informed risk reclassification. This outcome will capture the practical impact of PRS integration on clinical decision-making and preventive care planning.
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