在WISDOM研究中大规模整合乳腺癌多基因风险评分：一项全国性随机个性化筛查试验
Integrating breast cancer polygenic risk scores at scale in the WISDOM Study: a national randomized personalized screening trial.
作者信息
Fergus Kirkpatrick B, Heise Rachel S, Madlensky Lisa, Fiscalini Allison, Sabacan Leah, Theiner Sarah, Kapoor Shreya, Soto Irene A, Blanco Amie, Ross Katherine, Goodman-Gruen Deborah, Scheuner Maren, Hu Donglei, Heditsian Diane, Brain Susie, Arasu Vignesh A, Kaster Andrea, Chapa Lisa, Olopade Olufunmilayo I, Eklund Martin, Tice Jeffrey A, Ziv Elad, van 't Veer Laura, Esserman Laura J, Shieh Yiwey
机构信息
Department of Surgery, University of California, San Francisco, CA, USA.
Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
出版信息
Genome Med. 2025 Aug 28;17(1):97. doi: 10.1186/s13073-025-01524-7.
BACKGROUND
The Women Informed to Screen Depending On Measures of risk (WISDOM) Study is the first prospective, population-wide application of personalized breast cancer screening. We aim to demonstrate the feasibility of the study's novel use of polygenic risk scores (PRSs) to tailor screening, evaluate our strategy for adapting PRSs to diverse populations, and quantify the impact of incorporating PRS on the study's screening recommendations.
METHODS
WISDOM is a randomized, preference-tolerant screening trial in the USA testing the safety and morbidity of risk-based versus annual screening in women aged 40-74 without a prior history of breast cancer. This early report includes participants in the risk-based arm only and compares screening recommendations generated by the Breast Cancer Surveillance Consortium (BCSC) clinical risk model alone versus the BCSC model modified by a PRS (BCSC-PRS). The main outcome of interest is the proportion of participants with a change in screening recommendation after integrating PRS for risk stratification.
RESULTS
In the risk-based arm, 21,631 participants received a PRS. Small but statistically significant differences in the PRS were seen between major racial and ethnic groups (p < 0.001), and higher PRS was associated with greater extent of family history (p < 0.001) and denser breasts (p < 0.001). BCSC-PRS risk estimates changed the screening recommendations for 14% of women aged 40-49 compared to BCSC alone and for 10% of women aged 50-74. Projected net screening encounters at the population level were similar for both age groups.
CONCLUSIONS
In a first-in-kind application of PRS to inform breast cancer screening approaches, we demonstrate feasibility for scaled implementation, moderate changes to individual screening recommendations, and minimal projected downstream burden on the healthcare system.
TRIAL REGISTRATION
Prospectively registered on ClinicalTrials.gov as NCT02620852 on 12/2/2015.
背景
“基于风险评估的女性乳腺癌筛查研究（WISDOM）”是首个在全人群中前瞻性应用个性化乳腺癌筛查的研究。我们旨在证明该研究创新性地使用多基因风险评分（PRS）来定制筛查的可行性，评估我们将PRS应用于不同人群的策略，并量化纳入PRS对研究筛查建议的影响。
方法
WISDOM是一项在美国进行的随机、允许偏好的筛查试验，测试40 - 74岁无乳腺癌病史女性基于风险的筛查与年度筛查的安全性和发病率。本早期报告仅纳入基于风险组的参与者，比较仅由乳腺癌监测联盟（BCSC）临床风险模型生成的筛查建议与由PRS修改的BCSC模型（BCSC - PRS）生成建议的差异。主要关注的结果是在纳入PRS进行风险分层后，筛查建议发生改变的参与者比例。
结果
在基于风险组中，21631名参与者获得了PRS。主要种族和族裔群体之间的PRS存在虽小但具有统计学意义的差异（p < 0.001），较高的PRS与更广泛的家族史（p < 0.001）和更致密的乳房（p < 0.001）相关。与仅使用BCSC模型相比，BCSC - PRS风险估计改变了14%的40 - 49岁女性和10%的50 - 74岁女性的筛查建议。两个年龄组在人群水平上预计的净筛查次数相似。
结论
在首次将PRS应用于指导乳腺癌筛查方法的研究中，我们证明了扩大实施的可行性、对个体筛查建议的适度改变以及对医疗保健系统预计的下游负担最小。
试验注册
于2015年12月2日在ClinicalTrials.gov上前瞻性注册，注册号为NCT02620852。
Zotero 插件