Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake

Phase 1

Completed

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

• Registration Number: NCT02517593
• 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 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

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 Timeline

• Study First Submitted: 2015-07-31
• Study First Submitted QC: 2015-08-04
• Study First Posted: 2015-08-07
• Study Start: 2016-03
• Primary Completion: 2019-12-01
• Study Completion: 2019-12-01
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-28
• Last Update Posted: 2020-12-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 151

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

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
Endocrine related quality of life scores at 1 year	1 year	Functional Assessment of Cancer Therapy (FACT) - Endocrine Subscale Quality of Life Tool
Endocrine related quality of life scores at 2 years	2 years	Functional Assessment of Cancer Therapy (FACT) - Endocrine Subscale Quality of Life Tool
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

Trial Locations

Locations (2)

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

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