Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake (GENRE)

Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake: A Pilot Study to Determine if a Polygenic Risk Score Influences the Decision to Accept Breast Cancer Preventive Medications (Tamoxifen, Raloxifene, or Exemestane) Amongst Non-BRCA Women at Risk

The primary aim of this study is to determine if the addition of an individual polygenic risk score (PRS), in addition to the standard National Cancer Institute's 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: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Genetic: Polygenic Risk Score

Detailed Description

This trial is a prospective pilot study looking to integrate a novel and retrospectively validated polygenic risk score (PRS), based on 77 Single Nucleotide Polymorphisms (SNPs), into a standard breast cancer prevention consultation for non-BRCA women. In order to be eligible for trial participation, women will need to have a BCRAT estimate of ≥3% for the 5 year risk of developing breast cancer (which corresponds to the United States Preventative Services Task Force threshold for moderate to strong benefit from breast cancer preventing medications such as tamoxifen or raloxifene.

At the time of the breast cancer prevention consultation, women will be offered participation in this study by a clinical trials nurse and informed written consent will be obtained. For consenting patients, a single 7 to 10 ml blood sample will be taken and couriered to the MAYO clinic for sample analysis and several surveys will be administered. One of the surveys will assess the participants understanding and intention to take or not take breast cancer preventing medications. The decision to take or not take a breast cancer preventing medication will be deferred until a subsequent follow up visit.

On the second visit, the PRS test results will be reviewed with the patient and a recommendation regarding preventive medications will be made. The PRS score will risk stratify patients into one of three lifetime risk categories of developing breast cancer (low risk (<15 % lifetime risk), above average risk (15 to <40% risk) and high risk (>40%)). Participants will then answer a second survey in which their understanding of their breast cancer risk and intention to take breast cancer preventing medications will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • CancerCare Manitoba
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women > 35 years old and < 75 years old

2. Women with either of the following:

   A. a 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 US Preventative Services Task Force (32); or B. Women with a IBIS (Tyrer-Cuzik) score for the 10 year risk of breast cancer of ≥5%

3. Able to participate in all aspects of the study
4. Understand and signed the study informed consent

Exclusion Criteria:

1. 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 <5% for the 10 year risk
2. Women with known BRCA1 and BRCA2 mutations
3. Women with known contra-indications to Tamoxifen, raloxifene or exemestane
4. Unable to give informed consent
5. Prior history of invasive breast cancer or ductal carcinoma in situ
6. At risk due to prior radiation therapy to the chest

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: PRS; Providing polygenic risk score (PRS)

Genetic: Polygenic Risk Score; A Polygenic Risk Score (PRS) is a blood based genetic test which assesses 77 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%).; Other Names: PRS

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	Measure Description	Time Frame
Proportion of patients who are taking preventive medications at year 1		1 year
Proportion of patients who are taking preventive medications at year 2		2 years
Endocrine related quality of life scores at 1 year	Functional Assessment of Cancer Therapy (FACT) - Endocrine Subscale Quality of Life Tool	1 year
Endocrine related quality of life scores at 2 years	Functional Assessment of Cancer Therapy (FACT) - Endocrine Subscale Quality of Life Tool	2 years

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: CancerCare Manitoba
• 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: March 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: July 31, 2015
• First Submitted That Met QC Criteria: August 4, 2015
• First Posted (Estimate): August 7, 2015

Study Record Updates

• Last Update Posted (Actual): December 30, 2020
• Last Update Submitted That Met QC Criteria: December 28, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer; BCRAT; IBIS; PRS; Tyrer-Cuzick
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 15-006204; CCM-003 (Other Identifier: CancerCare Manitoba)

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