Women Informed to Screen Depending on Measures of Risk (Wisdom Study)
NCT ID: NCT02620852
Last Updated: 2025-11-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
NA
100000 participants
INTERVENTIONAL
2016-08-31
2026-09-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Communicating Objective Risk for Personalized Decision Making About Mammography
NCT01686360
ENGAGED 2 Study: Experiences With Mammography Screening and Breast Density 2
NCT03029286
Genetic Risk Estimations for Influencing Decision Making in Women at High Risk of Breast Cancer, GENRE 2 Study
NCT04474834
Breast Cancer Risk Assessment in Women Aged 40-49
NCT03180086
Breast Cancer Screening Adherence for Women at Moderate Risk for Breast Cancer
NCT07076147
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
SCREENING
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Complete a health questionnaire
Complete a health history questionnaire.
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
Screening advice based on a comprehensive risk assessment
Receive a screening schedule recommendation
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.
Complete a health questionnaire
Complete a health history questionnaire.
Screening advice based on a basic risk assessment
Receive a screening schedule recommendation
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Complete a health questionnaire
Complete a health history questionnaire.
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
Screening advice based on a comprehensive risk assessment
Receive a screening schedule recommendation
Screening advice based on a basic risk assessment
Receive a screening schedule recommendation
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
2. Prior prophylactic bilateral mastectomy
3. Inability to provide consent
4. Non-English or Spanish proficiency (Spanish participation available: June 2019)
30 Years
74 Years
FEMALE
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Patient-Centered Outcomes Research Institute
OTHER
Robert Wood Johnson Foundation
OTHER
Color Genomics, Inc.
INDUSTRY
Salesforce
UNKNOWN
National Cancer Institute (NCI)
NIH
Safeway Foundation
UNKNOWN
United States Department of Defense
FED
Breast Cancer Research Foundation
OTHER
University of California, San Francisco
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Laura Esserman, MD, MBA
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Alabama at Birmingham
Birmingham, Alabama, United States
University of California Irvine
Irvine, California, United States
University of California Los Angeles
Los Angeles, California, United States
University of California Davis
Sacramento, California, United States
University of California San Diego
San Diego, California, United States
University of California San Francisco
San Francisco, California, United States
TopLine MD Alliance
Miami, Florida, United States
University of Chicago
Chicago, Illinois, United States
Louisiana State University
New Orleans, Louisiana, United States
Weill Cornell Medicine
New York, New York, United States
Edith Sanford Breast Center
Sioux Falls, South Dakota, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Esserman LJ, Thompson IM, Reid B, Nelson P, Ransohoff DF, Welch HG, Hwang S, Berry DA, Kinzler KW, Black WC, Bissell M, Parnes H, Srivastava S. Addressing overdiagnosis and overtreatment in cancer: a prescription for change. Lancet Oncol. 2014 May;15(6):e234-42. doi: 10.1016/S1470-2045(13)70598-9.
Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand HS. Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst. 1999 Sep 15;91(18):1541-8. doi: 10.1093/jnci/91.18.1541.
Parmigiani G, Berry D, Aguilar O. Determining carrier probabilities for breast cancer-susceptibility genes BRCA1 and BRCA2. Am J Hum Genet. 1998 Jan;62(1):145-58. doi: 10.1086/301670.
Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004 Apr 15;23(7):1111-30. doi: 10.1002/sim.1668.
Claus EB. Risk models used to counsel women for breast and ovarian cancer: a guide for clinicians. Fam Cancer. 2001;1(3-4):197-206. doi: 10.1023/a:1021135807900.
Ozanne EM, Annis C, Adduci K, Showstack J, Esserman L. Pilot trial of a computerized decision aid for breast cancer prevention. Breast J. 2007 Mar-Apr;13(2):147-54. doi: 10.1111/j.1524-4741.2007.00395.x.
Darabi H, Czene K, Zhao W, Liu J, Hall P, Humphreys K. Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement. Breast Cancer Res. 2012 Feb 7;14(1):R25. doi: 10.1186/bcr3110.
Fergus KB, Heise RS, Madlensky L, Fiscalini A, Sabacan L, Theiner S, Kapoor S, Soto IA, Blanco A, Ross K, Goodman-Gruen D, Scheuner M, Hu D, Heditsian D, Brain S, Arasu VA, Kaster A, Chapa L, Olopade OI, Eklund M, Tice JA, Ziv E, van 't Veer L, Esserman LJ, Shieh Y; Athena/WISDOM Network Collaborators and Advocate Partners. Integrating breast cancer polygenic risk scores at scale in the WISDOM Study: a national randomized personalized screening trial. Genome Med. 2025 Aug 28;17(1):97. doi: 10.1186/s13073-025-01524-7.
Leggat-Barr K, Ryu R, Hogarth M, Stover-Fiscalini A, Veer LV', Park HL, Lewis T, Thompson C, Borowsky A, Hiatt RA, LaCroix A, Parker B, Madlensky L, Naeim A, Esserman L. Early Ascertainment of Breast Cancer Diagnoses Comparing Self-Reported Questionnaires and Electronic Health Record Data Warehouse: The WISDOM Study. JCO Clin Cancer Inform. 2023 Aug;7:e2300019. doi: 10.1200/CCI.23.00019.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NCI-2018-00562
Identifier Type: REGISTRY
Identifier Source: secondary_id
16752
Identifier Type: OTHER
Identifier Source: secondary_id
PCS-1402-10749
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.