Implementing Polygenic Risk Scores for Breast Cancer Prevention: a Feasibility Study (MIG)

July 31, 2026 updated by: Stefania Boccia, Catholic University of the Sacred Heart

Implementing Polygenic Risk Scores for Breast Cancer Prevention: Protocol for a Feasibility Study in a Real-world Clinical Setting

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will test the feasibility of integrating polygenic risk scores (PRS) into the CanRisk breast cancer risk model in a real-world clinical setting at Fondazione Policlinico Universitario Agostino Gemelli IRCCS. By embedding PRS testing into routine genetic counseling and patient care, the study aims to examine organizational, logistical, and patient-centered aspects of incorporating genomic data into breast cancer risk assessment.

Eligible participants include women with a family history of breast cancer, carriers of pathogenic variants included in CanRisk (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1), and women with unilateral breast cancer for controlateral risk assessment. Carriers of pathogenic variants not included in CanRisk (e.g., PTEN, TP53, CDH1) as well as women with bilateral breast cancer or ductal carcinoma in situ (DCIS), will be excluded, as CanRisk does not estimate risk for this condition.

All participants will provide a blood sample (9 mL in three K2EDTA tubes) for DNA extraction and SNP genotyping. PRS will be calculated using a 313-SNP array with ThermoFisher GeneTitan and the Axiom Precision Medicine Diversity Array, followed by standard quality control and genotype imputation. Results will be integrated into the CanRisk model previously calculated without PRS, to provide individualized risk estimates, in combination with clinical, anthropometric, and family history variables systematically collected for every participant.

Participants who request their CanRisk with PRS results will receive an email report approximately within one month of sample collection, summarizing their CanRisk estimates with and without PRS, and will be invited to complete a questionnaire on comprehension, perception, and emotional impact of the result. If the PRS leads to a change in risk classification, the case will be reviewed in a multidisciplinary discussion and the prevention plan may be modified accordingly. Participants who accept to be enrolled in the study but decline to receive their PRS results will be asked their reason, which will be documented verbatim.

Primary outcome:

Feasibility of CanRisk+PRS pathway assessment, measured by a 27-item Care Process Self-Evaluation Tool (CPSET) validated questionnaire, completed by both participants and healthcare staff at the end of the study.

Secondary outcomes:

  1. Uptake of CanRisk+PRS pathway
  2. Risk understanding and emotional impact, assessed using a validated questionnaire (Woof et al.)
  3. Risk reclassification rate, after PRS integration in the CanRisk model assessment
  4. Changes in breast cancer preventive pathway, recommended following multidisciplinary evaluation after CanRisk+PRS-based risk reclassification
  5. Impact on overall distribution across risk categories after PRS integration

This study will generate evidence on the clinical, technical, and organizational feasibility of integrating PRS into breast cancer risk assessment, informing the future implementation of personalized prevention programs.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Roma, Italy
        • Recruiting
        • Policlinico Universitario Fondazione Agostino Gemelli
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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)

  • Healthy women with:

    1. Known family history of breast cancer, or
    2. Known familiarity with carriers of pathogenic variants for genes included in the CanRisk model (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1), or
    3. Known carriers of pathogenic variants for genes included in the CanRisk model (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1)

  • Affected women with:

    1. Diagnosis of unilateral breast cancer
    2. Personal history of ovarian cancer

Exclusion Criteria:

  • 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
  • Participation in interventional clinical trials for breast cancer prevention in the last 12 months
  • Carriers or relatives of carriers of pathogenic variants in genes not included in the CanRisk model (genes other than BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51D, RAD51C, BARD1)
  • Inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Integrated PRS-enhanced breast cancer risk assessment
Women attending a Medical Genetics Clinic for breast cancer risk assessment, all undergoing CanRisk evaluation with and without PRS, without allocation to different interventions.
Genetic: Clinical pathway for breast cancer prevention based on PRS-integrated CanRisk assessment
Standard 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.).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of implementing an integrated clinical pathway including PRS
Time Frame: At 12 months from enrollment
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.
At 12 months from enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Uptake of CanRisk+PRS integrated pathway
Time Frame: At the time of enrollment, when eligible participants are offered PRS testing

Proportion of women accepting PRS testing among those offered:

(Number accepting PRS / Number offered PRS) × 100
At the time of enrollment, when eligible participants are offered PRS testing
Proportion of women requesting their individual CanRisk+PRS result
Time Frame: At month 12.
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.
At month 12.
Percentage of women reclassified into different risk categories after PRS integration
Time Frame: At month 12
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.
At month 12
Proportion of women with modified prevention pathways after PRS-informed reclassification
Time Frame: At month 12.
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.
At month 12.
Perception of risk and psychological impact
Time Frame: At month 12
Evaluation of women's understanding and perception of their personal breast cancer risk, as well as the emotional and psychological impact of risk communication, after receiving their CanRisk+PRS result. This will be assessed using the validated questionnaire by Woof et al., which specifically measures comprehension of risk estimates and associated emotional responses.
At month 12
Global redistribution of risk categories after PRS integration
Time Frame: At month 12.
The overall distribution of women across predefined breast cancer risk categories (low, moderate, high) before and after incorporating PRS into CanRisk. This outcome will provide a population-level view of how PRS influences breast cancer risk stratification and the extent of shifts in the global risk profile of the cohort.
At month 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Catholic University of the Sacred Heart

Collaborators

Catholic University of the Sacred Heart

Investigators

  • Principal Investigator: Stefania Boccia, Phd, Life Sciences and Public Health Department, Università Cattolica del Sacro Cuore, Rome, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

March 27, 2025

First Submitted That Met QC Criteria

April 3, 2025

First Posted (Actual)

April 10, 2025

Study Record Updates

Last Update Posted (Actual)

August 3, 2026

Last Update Submitted That Met QC Criteria

July 31, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7310
  • No. D.D. 931 (Other Grant/Funding Number: Italian National Complementary Plan PNC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All de-identified individual participant data (IPD) that underlie the published results of the study will be shared. This includes baseline demographics, clinical assessments, PRS test results (based on 313 SNPs), and questionnaire responses. Data will be made available via a secure Figshare repository upon study completion, with access governed by standard data use agreements to ensure participant confidentiality.

IPD Sharing Time Frame

After publication of the study results and will remain available indefinitely.

IPD Sharing Access Criteria

Researchers wishing to access the de-identified individual participant data (IPD) and supporting documentation must submit a formal request that includes a research proposal outlining the planned analyses and justification for data use. All requests will be reviewed by the study's Data Access Committee to ensure that the proposed research meets ethical and scientific criteria. A data sharing agreement, detailing the conditions for data use and protecting participant confidentiality, must be signed before access is granted. Detailed submission instructions and contact information will be provided on the secure repository platform.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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