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

May 28, 2025 updated by: Boccia Stefania

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

The goal of this single-arm interventional study is to learn whether integrating a polygenic risk score (PRS) into the CanRisk model can help improve breast cancer risk prediction and prevention in adult women with or without a family history of breast cancer and in women diagnosed with unilateral breast cancer. The main questions it aims to answer are:

  1. Is it feasible and acceptable to add PRS testing into standard breast cancer risk assessment for healthcare professionals and patients?
  2. Does PRS testing change the way individuals are categorized into low, moderate, or high-risk groups?
  3. What practical barriers or facilitators do participants and healthcare staff identify when using PRS in a routine clinical setting?

Participants will:

  • Provide a blood sample for PRS testing and for pathogenetic variants for breast cancer risk (if they have not already had genetic testing).
  • Complete a questionnaire on their experience and acceptance of PRS.

Because this is a single-arm study, there is no separate comparison group. The study team will use the results to see how well PRS can be integrated into clinical care and whether it offers any improvements in prevention strategies for breast cancer.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This single-arm feasibility study will integrate polygenic risk scores (PRS) into the CanRisk breast cancer risk model and evaluate the logistical and organizational aspects of its use in an established clinical setting. By embedding PRS testing into routine patient visits at the Fondazione Policlinico Universitario Agostino Gemelli, the study aims to examine how well these genomic data can be incorporated into existing workflows for breast cancer risk assessment.

Enrolled participants (both healthy individuals with a familial predisposition and those with unilateral breast cancer) will receive standard genetic counseling, including testing for known high-penetrance mutations if not already completed. In addition, they will be offered PRS testing using a SNP-based assay, which aggregates multiple low-penetrance genetic variants to refine the risk estimate provided by CanRisk. All molecular analyses will be performed under standardized laboratory protocols to ensure consistent quality control (QC), including genotyping and imputation steps.

Key technical procedures include:

Blood sample collection (≥0.5 mL) for DNA extraction and SNP genotyping using a commercially available array.

Genetic data management and QC, encompassing alignment to reference panels, imputation of missing genotypes, and filtering out low-frequency variants or those failing QC thresholds.

Integration of PRS results into the patient's risk profile alongside clinical, familial, and lifestyle factors already captured by CanRisk.

Study staff will document any changes (such as shifts in risk category) that occur once PRS results are factored in, as well as any modifications to the care pathway. Feasibility will be assessed using process metrics (e.g., number of participants offered PRS and acceptance rates, time from sample collection to result communication) and through structured questionnaires to both patients and healthcare professionals. These questionnaires capture impressions of risk communication clarity, perceived utility of the PRS, and any challenges or facilitators identified when introducing this genomic tool into routine practice.

Questionnaire to patients:

  • Communication with Patients and Families:

    1. Adequate time is allocated to explain PRS tests to patients and their families.
    2. Dedicated time is scheduled for genetic counseling sessions.
    3. Sufficient time is provided to explain the combined genetic and PRS results.
    4. The patients are well informed about their personalized risk assessment.

  • Collaboration with Territorial Services:

    4. General practitioners are informed about the implementation of PRS. 5. There is good coordination between the genetics clinic and primary care. 6. There are clear communication channels between specialists and general practitioners.

Questionnaire to healthcare professionals.

- Patient-centred organization:

  1. There is a patient-centered vision for genetic risk assessment within the organization.
  2. The quality of genetic counseling and PRS testing is a priority within the organization.
  3. The genetic counseling coordinator has a patient-centered vision.
  4. The communication of genetic test results and PRS scores is considered important.
  5. The organizational structure supports integrated genetic testing services.

  6. There is a clear vision of the genetic testing policy throughout the hospital.

    - Care process coordination:

  7. The agreements regarding the PRS test workflow are respected.
  8. All team members understand the stages of genetic testing and PRS evaluation.
  9. There is an optimal timeline between genetic testing and PRS analysis.
  10. There are clear protocols for the management of biological samples for PRS testing.
  11. Team members are involved in the coordination of genetic and PRS testing.
  12. Patients receive clear information about the results of both the genetic tests and the PRS.

  13. Follow-up appointments (if applicable) are scheduled appropriately after the communication of results.

    - Monitoring and follow-up

  14. The quality indicators for PRS implementation are clearly defined.
  15. Patients' needs are systematically monitored during the testing process.
  16. Patient satisfaction with combined genetic and PRS testing is monitored.
  17. The objectives of the integrated risk assessment are explicitly described.
  18. There is a monitoring system in place to verify the completion of all testing phases.
  19. The results of the combined risk assessment are systematically tracked.
  20. Variations in PRS results are monitored and documented.
  21. Risk communication processes are systematically evaluated.
  22. The entire testing process is continuously monitored and adjusted.

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

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
  • CanRisk score (without PRS) > 5% (calculated on www.canrisk.org)

  • Healthy women with:

    1. Known family history of breast cancer, or
    2. Known family history of genetic conditions associated with increased breast cancer risk, or
    3. Known carriers of pathogenic variants (BRCA1, BRCA2, PALB2, CHEK2, ATM, PTEN, TP53, CDH1)

  • Affected women with:

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

Exclusion Criteria:

  • CanRisk score (without PRS) < 5% (calculated on www.canrisk.org)
  • Diagnosis or history of bilateral breast cancer
  • 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
  • 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 arm
Participants in this experimental (signle) arm will undergo an integrated breast cancer risk assessment combining the CanRisk model with polygenic risk score (PRS) testing. The intervention includes genetic counseling, blood collection for PRS analysis, and a comprehensive risk evaluation. Additionally, participants will complete a questionnaire to gather their feedback on the integrated PRS clinical pathway.
Diagnostic test: Integrated PRS-Enhanced Breast Cancer Risk Assessment (CanRisk model)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of women accessing the pathway
Time Frame: At the time of participant enrollment in the clinical pathway for risk assessment.
At the time of participant enrollment in the clinical pathway for risk assessment.
Acceptance rate
Time Frame: At the time of enrollment, when eligible participants are offered PRS testing.
Percentage of women accepting PRS testing among those offered
At the time of enrollment, when eligible participants are offered PRS testing.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Qualitative assessment of PRS fesibility among healthcare professionals, using the CPSET questionnaire
Time Frame: At the end of the 12-month study period.

This outcome will be measured using the Care Process Self-Evaluation Tool (CPSET), a validated 29-item instrument developed to assess how the process of care is organized. Three subscales will be used:

  • Patient-focused organization;
  • Coordination of care;
  • Monitoring/follow-up of the care process. Each item is rated on a 1-10 scale and a higher total score indicates better organization of the care process. Subscale scores can also be reported to highlight specific areas of care process organization.
At the end of the 12-month study period.
Risk reclassification rate
Time Frame: Through study completion, up to 12 months.
Percentage of women whose risk classification changes after PRS integration, (comparing risk category assessed at baseline and reassessed after PRS analysis is complete).
Through study completion, up to 12 months.
Distribution of participants across low, moderate, and high breast cancer risk categories before and after integration of PRS
Time Frame: Through study completion, up to 12 months (the final distribution is calculated once all participants have received their PRS results).
This outcome measure assesses the distribution of participants across the three risk categories (low, moderate, high) prior to PRS integration, followed by the distribution after PRS results have been incorporated. The number and proportion of participants in each category will be determined, and any changes in distribution attributed to PRS will be evaluated.
Through study completion, up to 12 months (the final distribution is calculated once all participants have received their PRS results).
Qualitative assessment of PRS feasibility among patients, using CPSET questionnaire
Time Frame: Immediately after receiving their genetic counseling (on average 2-4 weeks after enrollment).

This outcome will be measured using the Care Process Self-Evaluation Tool (CPSET), a validated 29-item instrument developed to assess how the process of care is organized. The CPSET evaluates two subscales (for patients):

  • Communication with patients and families;
  • Cooperation with primary care. Each item is rated on a scale from 1 to 10, and a higher total score indicates better organization of the care process. Subscale scores can also be reported to highlight specific areas of care process organization.
Immediately after receiving their genetic counseling (on average 2-4 weeks after enrollment).

Collaborators and Investigators

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

Sponsor

Boccia Stefania

Collaborators

Catholic University of the Sacred Heart

Investigators

  • Principal Investigator: Stefania Boccia, Phd, Dipartimento di Scienze della Vita e Sanità Pubblica, 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 (Estimated)

June 9, 2025

Primary Completion (Estimated)

March 31, 2026

Study Completion (Estimated)

May 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)

June 3, 2025

Last Update Submitted That Met QC Criteria

May 28, 2025

Last Verified

May 1, 2025

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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