Genetic Risk Estimations for Influencing Decision Making in Women At High Risk of Breast Cancer, GENRE 2 Study

• Conditions: Breast Cancer
• Interventions: Genetic: Polygenic Risk Score

• Registration Number: NCT04474834
• Lead Sponsor: Mayo Clinic

Brief Summary

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.

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 Timeline

• Study Start: 2019-10-17
• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-14
• Study First Posted: 2020-07-17
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Primary Completion: 2029-12-15
• Study Completion: 2029-12-15

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Female
• Target Recruitment: 900

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PRS	Polygenic Risk Score	Providing polygenic risk score (PRS)

Primary Outcome Measures

Name	Time	Method
Patient self-reported intention to take a breast cancer preventing medication	up to 6 months after initial consultation

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (4)

Mayo Clinic; 🇺🇸 Jacksonville, Florida, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States