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Impact of Personalized Genetic Breast Cancer Risk Estimation With Polygenic Risk Scores on Preventive Endocrine Therapy Intention and Uptake.

Endocrine therapy (ET) is underutilized to reduce breast cancer (BC) incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 BC genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS BC risk prediction on intention to take and ET uptake among women recruited from BC clinics. Eligible participants had a 10-year BC risk >5% by Tyrer-Cuzick model (International Breast Cancer Intervention Study [IBIS]) or >3.0 % 5-year Gail Model risk with no BC history or hereditary BC syndrome. At baseline, BC calculators estimated risk, ET options were reviewed, and questionnaires assessed ET intent. After genotyping, PRS-updated BC risk estimates, ET options, and intent to take ET were reassessed; ET uptake was assessed during follow-up. From March 2016 to October 2017, 151 patients were enrolled (median [range] age, 56.1 [36.0-76.4] years). Median 10-year and lifetime IBIS risks were 7.9% and 25.3%. Inclusion of PRS increased lifetime IBIS BC risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased BC risk by PRS, 39 (41.9%) had greater intent to take ET; of those with decreased BC risk by PRS, 28 (46.7%) had less intent to take ET (P<.001). On multivariable regression, increased BC risk by PRS was associated with greater intent to take ET (P<.001). ET uptake was greater among participants with increased BC risk by PRS (53.4%) than with decreased risk (20.9%) (P<.001). PRS testing influenced intent to take and ET uptake. Assessing PRS effect on ET adherence is needed.

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