Abstract PD3-03: Impact of the breast cancer polygenic risk score on preventive endocrine therapy adherence and endocrine therapy usage on quality of life - The Genetic Risk Estimate (GENRE) trial
Authors: Pruthi Sandhya , Kim Julian O , Schaid Daniel , Cooke Andrew , Kim Christina , Goldenberg Benjamin , Sinnwell Jason , Grenier Debjani , Couch Fergus , Vachon Celine 
Published: March 2020

Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine therapy (ET) and yet drug uptake and adherence in this setting is suboptimal even among high risk women. A Polygenic Risk Score (PRS) comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)) can provide a personalized risk assessment and potentially influence ET adherence. We assessed ET adherence at 1 year comparing women whose risk estimate increased due to PRS versus women whose risk estimate decreased due to PRS. The effect of ET use on quality of life (hot flashes, night sweats, vaginal dryness, weight gain, joint pain) was evaluated.

Methods: Eligible women required either a 5 year Gail Model risk of ≥3% or 10 year IBIS ( International Breast Intervention Study or Tyrer-Cuzick model) of ≥5%. Women with a history of breast cancer (BC) or hereditary BC syndrome were excluded. High risk women were counseled at baseline using their Gail and IBIS risk scores and ET options were discussed including benefits and risks. Participants completed a self-reported questionnaire at baseline to assess their understanding of breast cancer risk and decision to take preventive ET. Blood samples were obtained and genotyped for 77 SNPs, and the odds ratio from the SNPs were used to modify the IBIS and Gail risk estimates. The BC -PRS risk estimate information was shared with study participants that reflected the IBIS and Gail risk estimates for 5 year, 10 year, & lifetime BC risk with and without the PRS. Follow up questionnaires at year 1 were administered to assess drug adherence and ET usage on quality of life.

Results: 151 women were enrolled at Mayo Clinic Rochester and CancerCare Manitoba from 2016 to 2017. The median age was 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian and 64.7% had&gt;1 family member with BC. Median 5yr, 10yr, & lifetime IBIS- PRS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). At year 1 (n=112 women) 46 % of those with an increase in risk when considering the BC-PRS score and 16 % with a decrease in risk were taking ET ( p&lt; 0.001). Types of ET taken: tamoxifen-18, raloxifene- 3, exemestane -14 and missing-1. Women taking ET reported weight gain ( 19.4% vs 6.7%, p=0.04) and more joint pain ( 27.8 % vs 12%, p=0.04) when compared to women not taking ET.

Conclusion: In high risk women, BC-PRS risk estimates in addition to standard BC risk calculators had a significant impact on preventive ET adherence. ET use was associated with weight gain and joint pain.

Citation Format: Sandhya Pruthi, Julian O Kim, Daniel Schaid, Andrew Cooke, Christina Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Fergus Couch, Celine Vachon. Impact of the breast cancer polygenic risk score on preventive endocrine therapy adherence and endocrine therapy usage on quality of life - The Genetic Risk Estimate (GENRE) trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-03.