Impact of a breast cancer (BC) polygenic risk score (PRS) on the decision to take preventive endocrine therapy (ET): The Genetic Risk Estimate (GENRE) trial.

Authors

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Julian Oliver Kim

Dept of Radiation Oncology, CancerCare Manitoba, Winnipeg, MB, Canada

Julian Oliver Kim , Daniel J. Schaid , Andrew Cooke , Christina Kim , Benjamin Adam Goldenberg , W Edward Highsmith Jr., Debjani Grenier , Jason P. Sinnwell , Amy C. Degnim , Fergus Couch , Celine M Vachon , Sandhya Pruthi

Organizations

Dept of Radiation Oncology, CancerCare Manitoba, Winnipeg, MB, Canada, Mayo Clinic, Rochester, MN, Dept of Medical Oncology, CancerCare Manitoba, Winnipeg, MB, Canada, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

Research Funding

Other Foundation

Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very few at-risk women choose to take them. A woman’s perceived BC risk correlates with uptake of ET. A PRS comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP) improves the accuracy of risk prediction for BC. We examined the impact of the addition of individualized PRS BC risk prediction to standard risk calculator estimates on intent to take BC prevention medication. Methods: Eligible women had ≥5% 10 yr BC Tyrer-Cuzick risk (IBIS) or 5 year Gail score ≥3%, with no history of BC or hereditary BC syndrome. Standard BC risk estimates (IBIS or Gail) were incorporated into the counselling on BC preventive ET. A self-reported questionnaire at baseline quantified intention to take ET and explored factors associated with this decision. Blood samples were obtained and genotyped for 77 SNPs, individualized PRS were calculated then incorporated into IBIS and Gail predictions for 5 yr, 10 yr, & lifetime BC risk. At a second visit, PRS risk & prevention recommendations were revisited. Post visit questionnaires assessed change in intent to take ET. Multivariable linear regression was performed to assess impact of baseline variables on change in intent to take medication. Results: From 2016 to 2017, 151 women in Canada & USA were enrolled, median age: 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian. Median 5yr, 10yr, & lifetime IBIS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). PRS increased BC risk estimates in 84 (55.6%) and reduced BC risk estimates in 67 (44%) women. After PRS risk counselling, intention to take ET significantly changed (p<0.001): 41.9% of those with increased PRS were more inclined, and 46.7% of women with decreased PRS were less inclined to take ET. On multivariable regression, increase in PRS (p<0.0001) and less concern about ET side effects (p<0.0001) were associated with greater intent to take ET. Conclusions: In high risk women, PRS significantly changed BC risk estimates & intent to take preventive ET. Further assessments of the impact of PRS scores on compliance with ET are warranted. Clinical trial information: NCT02517593

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Cancer Prevention, Hereditary Genetics, and Epidemiology

Track

Prevention, Risk Reduction, and Genetics

Sub Track

Cancer Prevention

Clinical Trial Registration Number

NCT02517593

Citation

J Clin Oncol 37, 2019 (suppl; abstr 1501)

DOI

10.1200/JCO.2019.37.15_suppl.1501

Abstract #

1501

Abstract Disclosures