Abstract
Endocrine therapy is underutilized to reduce breast cancer incidence among women at increased risk. Polygenic risk scores (PRSs) assessing 77 breast cancer genetic susceptibility loci personalizes risk estimates. We examined effect of personalized PRS breast cancer risk prediction on intention to take and endocrine therapy uptake among women at increased risk. Eligible participants had a 10-year breast cancer risk ≥5% by Tyrer-Cuzick model [International Breast Cancer Intervention Study (IBIS)] or ≥3.0 % 5-year Gail Model risk with no breast cancer history or hereditary breast cancer syndrome. Breast cancer risk was estimated, endocrine therapy options were discussed, and endocrine therapy intent was assessed at baseline. After genotyping, PRS-updated breast cancer risk estimates, endocrine therapy options, and intent to take endocrine therapy were reassessed; endocrine therapy 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 breast cancer risk estimates for 81 patients (53.6%) and reduced risk for 70 (46.4%). Of participants with increased breast cancer risk by PRS, 39 (41.9%) had greater intent to take endocrine therapy; of those with decreased breast cancer risk by PRS, 28 (46.7%) had less intent to take endocrine therapy (P < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy (P < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; P < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed.Prevention Relevance: Counseling women at increased breast cancer risk using polygenic risk score (PRS) risk estimates can significantly impact preventive endocrine therapy uptake. Further development of PRS testing to personalize breast cancer risk assessments and endocrine therapy counselling may serve to potentially reduce the incidence of breast cancer in the future.
Highlights
Prospective randomized controlled trials and meta-analyses (1) support the use of selective estrogen receptor modulators, including tamoxifen (2,3) and raloxifene (4), and aromatase inhibitors, including exemestane (5) and anastrozole (6), as means to reduce breast cancer (BC) incidence among women at increased risk
We examined effect of personalized polygenic risk score (PRS) BC risk prediction on intention to take and Endocrine therapy (ET) uptake among women recruited from BC clinics
The distribution of percentage change from the International Breast Cancer Intervention Study (IBIS) lifetime BC risk estimate with the addition of PRS was bidirectional in nature
Summary
Prospective randomized controlled trials and meta-analyses (1) support the use of selective estrogen receptor modulators, including tamoxifen (2,3) and raloxifene (4), and aromatase inhibitors, including exemestane (5) and anastrozole (6), as means to reduce breast cancer (BC) incidence among women at increased risk. In 2015, a large-scale genome-wide association study (GWAS) (18) yielded a SNP77 PRS that was strongly associated with BC, providing effective risk stratification of women with and without a family history of BC. This PRS has been shown to be a strong risk factor for BC independent of clinical risk factors and in high-risk populations, including women taking tamoxifen in the National Surgical Adjuvant Breast and Bowel Project P1/P2 (19) and those with dense breasts (20,21). We sought 1) to determine whether the addition of PRS to legacy clinical BC prediction tools influences a woman’s intention to take ET and ET uptake for BC risk reduction and 2) to explore the factors associated with that decision
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