Genetic Risk Estimation of Breast Cancer Prior to Preventive Medication Uptake

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.

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