Kim Julian O, Schaid Daniel J, Vachon Celine M, Cooke Andrew, Couch Fergus J, Kim Christina A, Sinnwell Jason P, Hasadsri Linda, Stan Daniela L, Goldenberg Benjamin, Neal Lonzetta, Grenier Debjani, Degnim Amy C, Thicke Lori A, Pruthi Sandhya
Department of Radiation Oncology, CancerCare Manitoba, Winnipeg, Manitoba, Canada.
Research Institute in Oncology and Hematology, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
Cancer Prev Res (Phila). 2021 Feb;14(2):175-184. doi: 10.1158/1940-6207.CAPR-20-0154. Epub 2020 Oct 23.
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 ( < 0.001). On multivariable regression, increased breast cancer risk by PRS was associated with greater intent to take endocrine therapy ( < 0.001). Endocrine therapy uptake was greater among participants with increased breast cancer risk by PRS (53.4%) than with decreased risk (20.9%; < 0.001). PRS testing influenced intent to take and endocrine therapy uptake. Assessing PRS effect on endocrine therapy adherence is needed. 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.
在内分泌风险增加的女性中，内分泌治疗在降低乳腺癌发病率方面未得到充分利用。评估77个乳腺癌遗传易感性位点的多基因风险评分（PRS）可实现风险估计的个性化。我们研究了个性化PRS乳腺癌风险预测对内分泌风险增加女性接受内分泌治疗的意愿和实际接受情况的影响。符合条件的参与者根据泰勒-库齐克模型[国际乳腺癌干预研究（IBIS）]的10年乳腺癌风险≥5%，或根据盖尔模型的5年风险≥3.0%，且无乳腺癌病史或遗传性乳腺癌综合征。在基线时评估乳腺癌风险，讨论内分泌治疗方案，并评估接受内分泌治疗的意愿。基因分型后，重新评估更新PRS后的乳腺癌风险估计、内分泌治疗方案以及接受内分泌治疗的意愿；在随访期间评估内分泌治疗的实际接受情况。2016年3月至2017年10月，共招募了151名患者[年龄中位数（范围）为56.1（36.0 - 76.4岁）]。IBIS模型的10年和终生风险中位数分别为7.9%和25.3%。纳入PRS后，81名患者（53.6%）的终生IBIS乳腺癌风险估计增加，70名患者（46.4%）的风险降低。在PRS提示乳腺癌风险增加的参与者中，39名（41.9%）接受内分泌治疗的意愿更强；在PRS提示乳腺癌风险降低的参与者中，28名（46.7%）接受内分泌治疗的意愿更弱（P<0.001）。多变量回归分析显示，PRS提示乳腺癌风险增加与接受内分泌治疗的意愿更强相关（P<0.001）。PRS提示乳腺癌风险增加的参与者中，内分泌治疗的实际接受率（53.4%）高于风险降低的参与者（20.9%；P<0.001）。PRS检测影响了接受内分泌治疗的意愿和实际接受情况。有必要评估PRS对内分泌治疗依从性的影响。使用多基因风险评分（PRS）风险估计为乳腺癌风险增加的女性提供咨询，可能会显著影响预防性内分泌治疗的接受情况。进一步开发PRS检测以实现乳腺癌风险评估和内分泌治疗咨询的个性化，可能有助于未来降低乳腺癌的发病率。
