Implementing polygenic risk scores for breast cancer prevention: protocol for a feasibility study in a real-world clinical setting
5 affiliations
- 1Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy
- 2Section of Genomic Medicine, Department of Life Science and Public Health, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Rome, Italy
- 3Research Core Facilty Data Collection G-SteP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- 4Medical Genetics Unit, Department of Laboratory and Hematological Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- 5Department of Woman and Child Health and Public Health - Public Health Area, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma, Italy
Abstract
Introduction Polygenic risk scores (PRSs) enhance breast cancer risk prediction when integrated into multifactorial models such as CanRisk. However, evidence on the real-world feasibility of incorporating PRS into routine hereditary breast cancer pathways remains limited, particularly within southern European healthcare systems. This study aims to evaluate the feasibility and acceptability of integrating PRS into clinical risk assessment in a real-world setting in Italy.Methods and analysis This is a single-arm feasibility implementation study to be conducted in a real-world clinical setting at a large university hospital in Rome, Italy. A minimum of 100 women attending a Medical Genetics Clinic for breast cancer risk assessment will be enrolled. Eligible participants include unaffected women with family history or increased baseline risk and women with unilateral breast cancer undergoing contralateral risk assessment. Participants will undergo CanRisk assessment to estimate lifetime breast cancer risk, calculated with and without PRS integration, and subsequently classified into three risk categories according to regional guidelines: general population risk, moderate risk and high risk. The primary outcome is feasibility of PRS integration into the clinical workflow, assessed using a validated questionnaire administered to participants and healthcare professionals. Secondary outcomes include PRS uptake, acceptability of receiving PRS-informed risk estimates, emotional response, risk reclassification rates and potential modifications to preventive recommendations. Quantitative analyses will include descriptive statistics, paired comparisons and multivariable regression models; qualitative perceptions will be explored through structured questionnaires.Ethics and dissemination The first version of the study was approved by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS—Comitato Etico Territoriale Lazio Area 3 on 13 December 2024, with the current amended version approved on 11 September 2025 (approval reference ID 7310). Participation is voluntary and based on written informed consent. Findings will be disseminated through peer-reviewed publications, presentations at national and international conferences and engagement with clinical and public health stakeholders to inform the integration of genomic risk stratification into preventive pathways.Trial registration number NCT06922708.
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BibTeX
@article{farina2026implementing,
title = {{Implementing polygenic risk scores for breast cancer prevention: protocol for a feasibility study in a real-world clinical setting}},
author = {Sara Farina and Francesco Andrea Causio and Pietro Eric Risuleo and Alessandra Verduchi and Eleonora Pascucci and Alessandra Sabatelli and Riccardo Galarducci and Luigi Russo and Elena Sonnini and Tina Pasciuto and Rosarita Amore and Dario Arzani and Emanuela L Cordisco and Maurizio Genuardi and Roberta Pastorino and Stefania Boccia},
journal = {BMJ Open},
year = {2026},
month = oct,
doi = {10.1136/bmjopen-2026-121783},
url = {https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-121783},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Implementing polygenic risk scores for breast cancer prevention: protocol for a feasibility study in a real-world clinical setting
AU - Sara Farina
AU - Francesco Andrea Causio
AU - Pietro Eric Risuleo
AU - Alessandra Verduchi
AU - Eleonora Pascucci
AU - Alessandra Sabatelli
AU - Riccardo Galarducci
AU - Luigi Russo
AU - Elena Sonnini
AU - Tina Pasciuto
AU - Rosarita Amore
AU - Dario Arzani
AU - Emanuela L Cordisco
AU - Maurizio Genuardi
AU - Roberta Pastorino
AU - Stefania Boccia
PY - 2026
DA - 2026/10/23
JO - BMJ Open
DO - 10.1136/bmjopen-2026-121783
UR - https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-121783
AB - Introduction Polygenic risk scores (PRSs) enhance breast cancer risk prediction when integrated into multifactorial models such as CanRisk. However, evidence on the real-world feasibility of incorporating PRS into routine hereditary breast cancer pathways remains limited, particularly within southern European healthcare systems. This study aims to evaluate the feasibility and acceptability of integrating PRS into clinical risk assessment in a real-world setting in Italy.Methods and analysis This is a single-arm feasibility implementation study to be conducted in a real-world clinical setting at a large university hospital in Rome, Italy. A minimum of 100 women attending a Medical Genetics Clinic for breast cancer risk assessment will be enrolled. Eligible participants include unaffected women with family history or increased baseline risk and women with unilateral breast cancer undergoing contralateral risk assessment. Participants will undergo CanRisk assessment to estimate lifetime breast cancer risk, calculated with and without PRS integration, and subsequently classified into three risk categories according to regional guidelines: general population risk, moderate risk and high risk. The primary outcome is feasibility of PRS integration into the clinical workflow, assessed using a validated questionnaire administered to participants and healthcare professionals. Secondary outcomes include PRS uptake, acceptability of receiving PRS-informed risk estimates, emotional response, risk reclassification rates and potential modifications to preventive recommendations. Quantitative analyses will include descriptive statistics, paired comparisons and multivariable regression models; qualitative perceptions will be explored through structured questionnaires.Ethics and dissemination The first version of the study was approved by the Ethics Committee of Fondazione Policlinico Universitario A. Gemelli IRCCS—Comitato Etico Territoriale Lazio Area 3 on 13 December 2024, with the current amended version approved on 11 September 2025 (approval reference ID 7310). Participation is voluntary and based on written informed consent. Findings will be disseminated through peer-reviewed publications, presentations at national and international conferences and engagement with clinical and public health stakeholders to inform the integration of genomic risk stratification into preventive pathways.Trial registration number NCT06922708.
SN - 2044-6055
SN - 2044-6055
ER -