Women Informed to Screen Depending on Measures of Risk (Wisdom Study)

NCT02620852 | Recruiting DMC FDA Device

• 4 other identifiers: PCS-1402-10749NCI-2018-00562R01CA237533-01A116752
• Study Type: interventional
• Target: 100,000
• Locations: 1 country
• Sites: 11

Brief Summary

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 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.

Conditions

Breast Cancer Screening; Breast Carcinoma in Situ; Breast Cancer

Keywords

Breast screening; mammography; prevention; risk assessment; DCIS; Breast cancer; Wisdom

Outcome Measures

Primary Outcomes (2)

• Late-stage cancer

  Proportion of cancers diagnosed at Stage IIB or higher

  5 years (minimum)

• Biopsy rate

  Rate of biopsies performed

  5 years (minimum)

Secondary Outcomes (12)

• Late-stage cancer rate and interval cancer rate

  5 years (minimum)

• Rate of stage IIA cancers

  5 years (minimum)

• Rate of systemic therapy

  5 years (minimum)

• Breast imaging rate

  5 years (minimum)

• Breast biopsy rate

  5 years (minimum)

Study Arms (2)

Annual Arm

ACTIVE COMPARATOR

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.

Other: Complete a health questionnaire; Other: Screening advice based on a basic risk assessment

Risk-Based Arm

EXPERIMENTAL

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.

Other: Complete a health questionnaire; Device: Provide a saliva sample for genetic testing; Other: Screening advice based on a comprehensive risk assessment

Interventions

Complete a health questionnaire OTHER

Complete a health history questionnaire.

Annual Arm; Risk-Based Arm

Provide a saliva sample for genetic testing DEVICE

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

Risk-Based Arm

Screening advice based on a comprehensive risk assessment OTHER

Receive a screening schedule recommendation

Risk-Based Arm

Screening advice based on a basic risk assessment OTHER

Receive a screening schedule recommendation

Annual Arm

Eligibility Criteria

• Age: 30 Years - 74 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female\*
• Age 30 years to 74 years old\*\*
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Patient-Centered Outcomes Research Institute: collaborator
• Robert Wood Johnson Foundation: collaborator
• Color Genomics, Inc.: collaborator
• Salesforce: collaborator
• National Cancer Institute (NCI): collaborator
• Safeway Foundation: collaborator
• United States Department of Defense: collaborator
• Breast Cancer Research Foundation: collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of California Irvine

Irvine, California, 92618, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California Davis

Sacramento, California, 95817, United States

RECRUITING

University of California San Diego

San Diego, California, 92093, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94115, United States

RECRUITING

TopLine MD Alliance

Miami, Florida, 33173, United States

RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

Louisiana State University

New Orleans, Louisiana, 70112, United States

ACTIVE NOT RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

Edith Sanford Breast Center

Sioux Falls, South Dakota, 57117, United States

ACTIVE NOT RECRUITING

Related Publications (11)

• 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.

  PMID: 24807866 BACKGROUND

• 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.

  PMID: 10491430 BACKGROUND

• 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.

  PMID: 9443863 BACKGROUND

• 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.

  PMID: 15057881 BACKGROUND

• 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.

  PMID: 14574179 BACKGROUND

• 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.

  PMID: 17319855 BACKGROUND

• 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.

  PMID: 22314178 BACKGROUND

• Fergus KB, Ross KS, Scheuner MT, Blanco AM, Tice JA, Ziv E, Shieh Y, van 't Veer L, Olopade OI, Goodman DL, Tong BS, Harvey H, DeRosa D, Risty L, Silver E, Kaster A, Fiscalini AS, Blum K, Heise R, Sabacan L, Heditsian D, Brain S, Petruse A, Eklund M, Hiatt RA, Borowsky AD, Naeim A, Park HL, LaCroix AZ, Parker BA, Lancaster R, Esserman J, Wenger N, Arasu V, Anton-Culver H, Esserman LJ, Madlensky L. Germline Pathogenic Variants Among Women Without a History of Breast Cancer: A Secondary Analysis of the WISDOM Randomized Clinical Trial. JAMA Intern Med. 2025 Dec 12:e257323. doi: 10.1001/jamainternmed.2025.7323. Online ahead of print.

  PMID: 41385723 DERIVED

• Esserman LJ, Fiscalini AS, Naeim A, Van't Veer LJ, Kaster A, Scheuner MT, LaCroix AZ, Borowsky AD, Anton-Culver H, Olopade OI, Esserman J, Lancaster R, Madlensky L, Blanco AM, Ross KS, Goodman DL, Tong BS, Hogarth M, Heditsian D, Brain S, Lee V, Blum K, Kim MO, Sabacan LP, Fergus KB, Yau C, Park HL, Parker BA, Kaplan C, Rhoads KF, Eder S, Adduci K, Matthews JB, Wenger NS, Shieh Y, Hiatt RA, Ziv E, Tice JA, Eklund M. Risk-Based vs Annual Breast Cancer Screening: The WISDOM Randomized Clinical Trial. JAMA. 2025 Dec 12:e2524784. doi: 10.1001/jama.2025.24784. Online ahead of print.

  PMID: 41385349 DERIVED

• 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.

  PMID: 40877879 DERIVED

• 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.

  PMID: 37607323 DERIVED

MeSH Terms

Conditions

Breast Carcinoma In Situ; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Carcinoma in Situ; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Laura Esserman, MD, MBA

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Allison Fiscalini, MPH

CONTACT

(415) 476-0267; allison.stoverfiscalini@ucsf.edu

Jennifer Atamer

CONTACT

Jennifer.atamer@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2015
• First Posted: December 3, 2015
• Study Start: August 31, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)