Affiliations of authors: Division of General Internal Medicine, Department of Medicine (YS, EZ, JAT), Department of Surgery (SDS, CKT, ASF, LJE), Department of Radiology (LJE), and Department of Laboratory Medicine, Helen Diller Family Comprehensive Cancer Center (LJvV), University of California, San Francisco, San Francisco, CA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (ME); Department of Family Medicine and Public Health, University of California, San Diego, San Diego, CA (LM).
J Natl Cancer Inst. 2017 Jan 27;109(5). doi: 10.1093/jnci/djw290. Print 2017 Jan.
Ongoing controversy over the optimal approach to breast cancer screening has led to discordant professional society recommendations, particularly in women age 40 to 49 years. One potential solution is risk-based screening, where decisions around the starting age, stopping age, frequency, and modality of screening are based on individual risk to maximize the early detection of aggressive cancers and minimize the harms of screening through optimal resource utilization. We present a novel approach to risk-based screening that integrates clinical risk factors, breast density, a polygenic risk score representing the cumulative effects of genetic variants, and sequencing for moderate- and high-penetrance germline mutations. We demonstrate how thresholds of absolute risk estimates generated by our prediction tools can be used to stratify women into different screening strategies (biennial mammography, annual mammography, annual mammography with adjunctive magnetic resonance imaging, defer screening at this time) while informing the starting age of screening for women age 40 to 49 years. Our risk thresholds and corresponding screening strategies are based on current evidence but need to be tested in clinical trials. The Women Informed to Screen Depending On Measures of risk (WISDOM) Study, a pragmatic, preference-tolerant randomized controlled trial of annual vs personalized screening, will study our proposed approach. WISDOM will evaluate the efficacy, safety, and acceptability of risk-based screening beginning in the fall of 2016. The adaptive design of this trial allows continued refinement of our risk thresholds as the trial progresses, and we discuss areas where we anticipate emerging evidence will impact our approach.
关于乳腺癌筛查的最佳方法，目前仍存在争议，这导致专业学会的推荐意见也不一致，尤其是对于 40 至 49 岁的女性。一种潜在的解决方案是基于风险的筛查，即根据个体风险来决定开始筛查的年龄、停止筛查的年龄、筛查的频率和方式，以最大限度地提高侵袭性癌症的早期发现率，并通过最佳资源利用来降低筛查的危害。我们提出了一种新的基于风险的筛查方法，该方法整合了临床风险因素、乳腺密度、代表遗传变异累积效应的多基因风险评分以及中、高度外显率种系突变的测序结果。我们展示了如何使用我们的预测工具生成的绝对风险估计阈值来对女性进行分层，以采用不同的筛查策略（每两年进行一次乳房 X 线摄影检查、每年进行一次乳房 X 线摄影检查、每年进行一次乳房 X 线摄影检查并辅以磁共振成像检查、目前推迟筛查），同时告知 40 至 49 岁女性开始筛查的年龄。我们的风险阈值和相应的筛查策略基于现有证据，但需要在临床试验中进行检验。一项实用的、基于偏好的、每年一次与个体化筛查的随机对照试验——Women Informed to Screen Depending On Measures of risk（WISDOM）研究，将研究我们提出的方法。WISDOM 将于 2016 年秋季开始，评估基于风险的筛查的疗效、安全性和可接受性。该试验的适应性设计允许随着试验的进行，不断完善我们的风险阈值，我们还讨论了预计新出现的证据将如何影响我们的方法的领域。
