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妇女被告知根据风险措施进行筛查（智慧研究） (WISDOM)

2026年9月17日 更新者：University of California, San Francisco

实现范式转变：个性化与年度乳腺癌筛查的偏好容忍 RCT（智慧研究）

Most physicians still use a one-size-fits-all approach to breast screening in which all women, regardless of their personal history, family history or genetics (except BReast CAncer gene (BRCA) carriers) are recommended to have annual mammograms starting at age 40. Mammograms benefit women by detecting cancers early when they are easier to treat, but they are not perfect. Recent news stories have discussed some of the potential harms: large numbers of positive results that cause stressful recalls for additional mammograms and biopsies. With the current screening approach, half of the women who undergo annual screening for ten years will have at least one false positive biopsy. Potentially more important are cancer diagnoses for growths that might never come to clinical attention if left alone (called "overdiagnosis"). This can lead to unnecessary treatment. Even more concerning is evidence that up to 20% of breast cancers detected today may fall into the category of "overdiagnosis."

The WISDOM 1.0 study compares annual screening with a risk-based breast cancer screening schedule, based upon each woman's personal risk of breast cancer. The investigators have designed the study to be inclusive of all, so that even women who might be nervous about being randomly assigned to receive a particular type of care (a procedure that is typical in clinical studies) will still be able to participate by choosing the type of care they receive.

For participants in the risk-based screening arm, each woman will receive a personal risk assessment that includes her family and medical history, breast density measurement and tests for genes (mutations and variations) linked to the development of breast cancer. Women who have the highest personal risk of developing breast cancer will receive more frequent screening, while women with a lower personal risk would receive less frequent screening. No woman will be screened less than is recommended by the USPSTF breast cancer screening guidelines.

If this study is successful, women will gain a realistic understanding of their personal risk of breast cancer as well as strategies to reduce their risk, and fewer women will suffer from the anxiety of false positive mammograms and unnecessary biopsies. The investigators believe this study has the potential to transform breast cancer screening in America.

Starting in Spring 2023, WISDOM's design shifted to remove the randomized option, but will continue with the preference/self-selection option for participation (WISDOM 2.0). Participants will therefore continue to choose their study arm (Personalized or Annual) rather than have the option to be randomized. This study design change was made after review of the WISDOM 1.0 data by an independent monitoring committee, which indicates that personalized screening does not cause harm. WISDOM 2.0 has also lowered the eligibility to ages 30-74. Women ages 30-39 will only be offered to join the Personalized Arm.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

For almost 30 years, annual mammograms for women over 40 have been a cornerstone of the US strategy to reduce mortality from breast cancer. A number of advances in the understanding of breast cancer biology, and screening in general, have led to calls to revise and improve national screening strategies (Esserman et al., 2014). In 2009, the US Preventive Services Task Force (USPSTF) introduced changes to screening guidelines, recommending that annual mammograms for all women 40-75 be replaced by biennial screening for women ages 50-75, and that screening in the 40's should be individualized by taking patient context into account, including the patient's values regarding specific benefits and harms. Despite being based on a thorough review of the scientific literature, these recommendations continue to spark debate and scientific opinion on the effectiveness of annual screening is greatly divided. On one hand the radiology and obstetrics/gynecology community argues that annual mammograms starting at 40 reduce the rate of interval cancers. On the other hand, primary care physicians and other specialists believe that annual screening results in more false-positives and unnecessary treatment and that a more targeted approach could result in fewer false-positives and less over-diagnosis without increasing the number of interval cancers. In fact it has been estimated that half of women will receive a false-positive recall over 10 years of annual screening and that as many as 20% of all breast cancers might be overdiagnosed. Since 2009 this debate has intensified, paralyzing the system and thwarting any efforts to change or improve screening. The end result is that women are frustrated and confused, and some have stopped screening altogether.

Despite a vastly improved understanding of breast cancer risk, the only criteria used to establish a woman's screening recommendations is her age (and BRCA status if known), but there are risk models available that incorporate personal and family history of breast disease, endocrine exposures and breast density to assess breast cancer risk (Constantino, et al., 1999; Parmigiani, et al., 1998; Tyrer, et al., 2004; Claus, et al., 2001; Ozanne, et al., 2003). Most recently certain genetic mutations and common genetic variants (single nucleotide polymorphisms or SNPs) have been confirmed predictors as well (Darabi, et al., 2012). Therefore, advances in this understanding of breast cancer biology, risk assessment, and imaging have enabled the creation of better tools and sufficient knowledge to replace the one-size-fits-all approach to screening and to implement a new, personalized model; one that provides recommendations on when to start, when to stop, and how often to screen that depend upon well characterized measures of risk.

The investigators propose to test a transformational evidence-based approach to breast screening that educates women about their actual risk, and tailors screening recommendations to them as individuals. Within the Athena Breast Health Network, the study will compare comprehensive, patient-centered risk-based screening to annual screening for women starting at age 40. The comprehensive risk assessment is based on a widely accepted risk model, the Breast Cancer Surveillance Consortium model, that includes endocrine exposures, family history and breast density, with additional genomic risk factors that include rare and uncommon major breast cancer susceptibility alleles as well as more common and recently validated single nucleotide polymorphisms (SNPs) that can, cumulatively, contribute significantly to a woman's individual risk. The study's personalized approach will recommend an age to start and stop screening as well as a frequency based upon individual risk. Women of highest risk will receive greater surveillance than those of lowest risk where the lower bound is the USPSTF recommended guidelines. In this manner, the study will focus the most effort on those most likely to develop the disease.

In close collaboration with patient advocates, the WISDOM 1.0 study has been designed as a 5-year, preference-tolerant, 65,000 patient, randomized controlled trial of risk-based versus annual screening. Individuals uncomfortable with the potential to be assigned to a particular arm in the randomized cohort can participate in the self-assigned observational cohort, an example of the pragmatic approach taken. Total accrual is anticipated to be 100,000 women across both cohorts. A broad group of stakeholders have participated in crafting this approach, including advocates, payers, the entire range of medical specialists and primary care providers and researchers involved with breast cancer screening across the entire Athena Network, technology partners, the Office of the President at the University of California, and policy-making organizations. WISDOM 1.0 trial was originally designed to randomize 65,000 women and be completed after five years to provide a median of ~3 years of exposure time in each randomized arm. However, due to slow initial accrual, trial duration was extended to up to ten years enabling a sample size reduction with maintained statistical power. The accrual goals were updated and approved by the Data Safety Monitoring Board (DSMB) and the Patient Centered Outcomes Research Institute.

The study hypothesizes that risk-based screening will be an improvement over annual screening because it will be as safe, less morbid, enable more cancer prevention, less stressful and more readily accepted by women as a result of an improved understanding of their personal risk.

The Athena Breast Health Network was established across the 5 University of California medical centers to develop a new, harmonized approach to breast cancer prevention, screening and treatment. Athena is among the few centers in North America to use technology to integrate risk assessment into breast screening. The investigators have developed a cadre of "breast health specialists" who provide women with counseling and support around risk and prevention. There are currently 100,000 registered Athena participants, with 30,000 new patients per year and growing with the addition of Sanford Health, one of the largest rural health networks in the country. The primary research mission of Athena is to address issues requiring a population-based approach and translate solutions to clinical practice. Athena is uniquely positioned to address the screening controversy and provide women with renewed confidence in decisions about their breast health. Risk-based screening for breast cancer is exactly the advanced, evidence-based approach to medicine described in the NIH and FDA's "Path to Personalized Medicine". If these hypotheses prove to be correct, this study will be able to establish a clear justification for its use, and provide a framework for widespread implementation that will benefit women across the country.

Starting in Spring 2023, WISDOM's design shifted to remove the randomized option, but will continue with the preference/self-selection option for participation (WISDOM 2.0). Participants will therefore continue to choose their study arm (Personalized or Annual) rather than have the option to be randomized. This study design change was made after review of the WISDOM 1.0 data by an independent monitoring committee, which indicates that personalized screening does not cause harm. WISDOM 2.0 has also lowered the eligibility to ages 30-74. Women ages 30-39 will only be offered to join the Personalized Arm.

研究类型

介入性

注册 (估计的)

100000

阶段

  • 不适用

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

研究联系人备份

学习地点

  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35294
        • 招聘中
        • University of Alabama at Birmingham
        • 接触：
        • 首席研究员：
          • Rachael Lancaster, MD
    • California
      • Irvine、California、美国、92618
        • 招聘中
        • University of California Irvine
        • 接触：
          • Hannah Park, PhD
          • 电话号码：949-824-2651
          • 邮箱：hlpark@uci.edu
        • 首席研究员：
          • Hoda Anton-Culver, PhD
      • Los Angeles、California、美国、90095
        • 招聘中
        • University of California Los Angeles
        • 接触：
        • 首席研究员：
          • Arash Naeim, MD, PhD
      • Sacramento、California、美国、95817
        • 招聘中
        • University of California Davis
        • 接触：
        • 首席研究员：
          • Alexander Borowsky, MD
      • San Diego、California、美国、92093
        • 招聘中
        • University of California San Diego
        • 副研究员：
          • Barbara Parker, MD
        • 副研究员：
          • Lisa Madlensky, PhD
        • 接触：
        • 首席研究员：
          • Sheri Hartman, PhD
      • San Francisco、California、美国、94115
        • 招聘中
        • University of California San Francisco
        • 首席研究员：
          • Laura van 't Veer, PhD
        • 接触：
    • Florida
      • Miami、Florida、美国、33173
    • Illinois
    • Louisiana
      • New Orleans、Louisiana、美国、70112
        • 主动，不招人
        • Louisiana State University
    • New York
      • New York、New York、美国、10021
        • 招聘中
        • Weill Cornell Medicine
        • 首席研究员：
          • Yiwey Shieh, MD
    • South Dakota
      • Sioux Falls、South Dakota、美国、57117
        • 主动，不招人
        • Edith Sanford Breast Center

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

30年 至 74年 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

女性

描述

Inclusion Criteria:

  1. Female*
  2. Age 30 years to 74 years old**
  3. Reside in the United States***

NOTE*: As of 2019, we are now enrolling all persons who identify as female, and will capture both their sex at birth and gender identity in the baseline survey.

NOTE**: Eligibility from 2016 - October 2023 included ages 40-74 (WISDOM 1.0) and expanded to age 30 in October 2023 (WISDOM 2.0).

NOTE***: As of 2019, recruitment is available nationwide. Original eligibility was limited to California, North Dakota, South Dakota, Iowa, Minnesota, Alabama, Louisiana, Illinois OR have coverage from a participating health plan.

Exclusion Criteria:

  1. Prior Breast cancer or ductal carcinoma in situ (DCIS) diagnosis
  2. Prior prophylactic bilateral mastectomy
  3. Inability to provide consent
  4. Non-English or Spanish proficiency (Spanish participation available: June 2019)

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：放映
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
有源比较器：Annual Arm

Women in this arm will receive Athena standard of care mammography screening, including annual mammograms. They will complete a health questionnaire and receive screening advice based on a basic risk assessment.
其他：Complete a health questionnaire

Complete a health history questionnaire.

其他：Screening advice based on a basic risk assessment

Receive a screening schedule recommendation
实验性的：Risk-Based Arm

Women in this arm will receive risk-based screening, where risk is calculated based on a model including personal history, family history, and genetic testing. All women in the risk-based arm complete a health questionnaire, provide a saliva sample for genetic testing, and receive screening advice based on a comprehensive risk assessment. Women in this arm will be tested for a panel of 9 genes related to breast cancer risk as well as a panel of SNPs, which can further modify risk. Women will be assigned a screening start date, screening stop date, and screening frequency.
其他：Complete a health questionnaire

Complete a health history questionnaire.

设备：Provide a saliva sample for genetic testing

Provide a saliva sample for testing of 9 genes and a panel of single nucleotide polymorphisms (SNPs) that influence breast cancer risk

其他：Screening advice based on a comprehensive risk assessment

Receive a screening schedule recommendation

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Late-stage cancer
大体时间：5 years (minimum)

Proportion of cancers diagnosed at Stage IIB or higher
5 years (minimum)
Biopsy rate
大体时间：5 years (minimum)

Rate of biopsies performed
5 years (minimum)

次要结果测量

结果测量
措施说明
大体时间
Late-stage cancer rate and interval cancer rate
大体时间：5 years (minimum)

Rate of Stage IIB or higher cancers and rate of interval (detected within 12-24 months of a normal screen) cancers
5 years (minimum)
Rate of stage IIA cancers
大体时间：5 years (minimum)

To assess the difference between the arms in the rate of stage IIA cancers (prognostic and anatomic), specifically to test for non-inferiority of personalized screening compared with annual screening with respect to detection rates of prognostic and anatomic stage IIA cancers.
5 years (minimum)
Rate of systemic therapy
大体时间：5 years (minimum)

Rate of systemic therapy as measure of morbidity
5 years (minimum)
Breast imaging rate
大体时间：5 years (minimum)

Breast imaging (Mammogram or MRI) rate as measure of morbidity
5 years (minimum)
Breast biopsy rate
大体时间：5 years (minimum)

Breast biopsy rate as measure of morbidity
5 years (minimum)
DCIS rate
大体时间：5 years (minimum)

Rate of ductal carcinoma in situ (DCIS) as a measure of morbidity, stratified by biologic type
5 years (minimum)
Chemoprevention uptake rate
大体时间：5 years (minimum)

Rate of uptake of endocrine prevention interventions
5 years (minimum)
Choice of risk-based versus annual screening in self-assigned cohort
大体时间：5 years (minimum)

Proportion of participants who choose risk-based versus annual screening in the self-assigned cohort as a measure of acceptability
5 years (minimum)
Adherence to assigned screening schedule
大体时间：5 years (minimum)

Proportion of participants who adhere to their assigned screening schedules as a measure of acceptability
5 years (minimum)
Breast-cancer anxiety
大体时间：5 years (minimum)

Breast cancer anxiety (as measured with the Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety scale) as a measure of acceptability
5 years (minimum)
Decisional regret
大体时间：5 years (minimum)

Decisional regret (as measured with the Decision Regret Scale, a 5-item Likert scale) as a measure of acceptability
5 years (minimum)
Ultra-low risk cancer rate
大体时间：5 years (minimum)

Rates of ultra-low risk cancer
5 years (minimum)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of California, San Francisco

合作者

Patient-Centered Outcomes Research Institute
National Cancer Institute (NCI)
United States Department of Defense
Robert Wood Johnson Foundation
Breast Cancer Research Foundation
Color Genomics, Inc.
Salesforce
Safeway Foundation

调查人员

  • 首席研究员：Laura Esserman, MD, MBA、University of California, San Francisco

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2016年8月31日

初级完成 (估计的)

2029年9月30日

研究完成 (估计的)

2029年9月30日

研究注册日期

首次提交

2015年12月1日

首先提交符合 QC 标准的

2015年12月2日

首次发布 (估计的)

2015年12月3日

研究记录更新

最后更新发布 (实际的)

2026年9月21日

上次提交的符合 QC 标准的更新

2026年9月17日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • PCS-1402-10749
  • NCI-2018-00562 (注册表标识符：NCI Clinical Trials Reporting Program (CTRP))
  • R01CA237533-01A1 (美国 NIH 拨款/合同)
  • 16752 (其他标识符：University of California, San Francisco)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

是的

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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