Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial
Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial
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DOI：
10.1093/jnci/djw290
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发表时间：
2017-05-01
影响因子：
10.3
通讯作者：
Tice, Jeffrey A.
中科院分区：
文献类型：
--
作者：
Shieh, Yiwey;Eklund, Martin;Tice, Jeffrey A.
关于乳腺癌筛查最佳方法的持续争议导致了不一致的专业社会建议，特别是在40至49岁的女性中。一个潜在的解决方案是基于风险的筛查，其中关于开始年龄，停止年龄，频率和筛查方式的决定是基于个体风险，以最大限度地早期发现侵袭性癌症，并通过最佳资源利用最大限度地减少筛查的危害。我们提出了一种新的方法，以风险为基础的筛选，整合临床风险因素，乳腺密度，多基因风险评分代表遗传变异的累积效应，和测序的中度和高度突变生殖系突变。我们展示了我们的预测工具生成的绝对风险估计阈值如何用于将女性分层为不同的筛查策略（两年一次的乳房X光检查，每年一次的乳房X光检查，每年一次的乳房X光检查与连续性磁共振成像，此时推迟筛查），同时告知40至49岁女性的筛查起始年龄。我们的风险阈值和相应的筛查策略是基于目前的证据，但需要在临床试验中进行测试。根据风险衡量标准进行筛查的女性（WISDOM）研究是一项务实的，偏好容忍的年度与个性化筛查的随机对照试验，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有效性、安全性和可接受性。本试验的适应性设计允许随着试验的进展继续改进我们的风险阈值，我们讨论了我们预计新出现的证据将影响我们方法的领域。
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.