Genetic Risk Estimations for Influencing Decision Making in Women at High Risk of Breast Cancer, GENRE 2 Study (GENRE2)

GENetic Risk Estimation of Breast Cancer Prior to Decisions on Preventive Therapy Uptake, Risk Reducing Surgery or Intensive Imaging Surveillance: A Study to Determine if a Polygenic Risk Score Influences the Decision Making Options Amongst High Risk Women (GENRE 2)

The primary aim of this study is to determine if the addition of an individual polygenic risk score (PRS) in addition to the Breast Cancer Risk Assessment Tool (BCRAT) or Tyrer-Cuzick (IBIS) score will aid women at risk of breast cancer in making a decision to take (or not take) medications to prevent breast cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: Polygenic Risk Score

Detailed Description

This is a minimal risk prospective multisite study with a single arm incorporating the PRS into a standard breast cancer risk reduction consultation, followed by annual surveys over 10 years to determine if and how the availability of the PRS influenced patient decisions regarding preventive medicine and medication compliance. Because women know beforehand that the PRS is pending, study participants will be advised that a final decision to take preventive medicine must be deferred until after the PRS results are made available. Nevertheless, a survey of understanding of risk and benefit and assessment of willingness to take preventive medicine will be done prior to receiving the PRS results and then another survey will be completed after receiving the PRS score.

• Study Type: Observational
• Enrollment (Actual): 737

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women attending the Mayo Clinic Breast Cancer clinics in Rochester, Arizona and Florida or the Mayo Clinic Health System in Austin or Albert Lea who meet eligibility criteria will be offered participation in this study after initial clinical calculation of the BCRAT or IBIS score and counseling as to the advisability of preventive therapy.

Description

Inclusion Criteria:

• Women >= 35 years old and =< 75 years old with at least one of the following:

  • A National Cancer Institute (NCI)-BCRAT 5 year risk of >= 3% which corresponds to the level in which there is moderate evidence of treatment benefit outweighing risk according to the United States (US) Preventative Services Task Force
  • IBIS (Tyrer-Cuzik) score for the 10 year risk of breast cancer of >= 5%
  • History atypical ductal hyperplasia or atypical lobular hyperplasia with a BCRAT >= 3% or IBIS >= 5%
  • History of lobular carcinoma in situ with a BCRAT >= 3% or IBIS >= 5% OR
• Women >= 18 years old or =< 75 years old with a BRCA 1 or 2 mutation, CHEK 2, PALB 2, ATM, or other hereditary breast mutation carrier per investigator
• Willing and able to provide an email address to receive study surveys
• Able to participate in all aspects of the study
• Understand and sign the study informed consent

Exclusion Criteria:

• Women whose BCRAT falls below the threshold (<3 % 5 year risk) of moderate benefit according to the US Preventative Task Force AND Women whose IBIS score is <8% for the 10 year risk
• Women with known contra-indications to Tamoxifen, raloxifene ,exemestane, or anastrazole
• Current or prior use of Tamoxifen, raloxifene, exemestane or anastrazole
• Unable to give informed consent
• Prior history of invasive breast cancer, ductal carcinoma in situ or other breast cancers
• At high risk due to prior radiation therapy to the chest
• Women who are pregnant or breastfeeding
• Prior risk reducing or prophylactic mastectomy
• Unwilling or unable to provide an email address for study surveys to be sent to
• Subject has a known history or any condition or factor judged by the investigator to preclude participation in the study or which might hinder adherence

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

PRS; Providing polygenic risk score (PRS)

Genetic: Polygenic Risk Score; A Polygenic Risk Score (PRS) is a blood based genetic test which assesses 300 common breast cancer susceptibility loci (Single Nucleotide Polymorphisms). The PRS has been retrospectively validated and categorizes women into three categories of lifetime risk of developing breast cancer: Low Risk (<15% lifetime risk), Above Average Risk (15 to 40%), and high risk (>40 %).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patient self-reported intention to take a breast cancer preventing medication	up to 6 months after initial consultation

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients who are taking preventative medications each year for 10 years	Each year for up to 10 years
Endocrine related quality of life scores each year for 10 years	Each year for up to 10 years
Proportion of patient who are pursuing supplemental screening for 10 years	Each year for up to 10 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Sandhya Pruthi, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Estimated): December 15, 2029
• Study Completion (Estimated): December 15, 2029

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; BRCA2; BRCA1; BRCA; BRCA 1/2; BCRAT; IBIS; PRS; Tyrer-Cuzick; CEDM
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 19-003085; NCI-2022-02838 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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