Evidence map›Paper›PMID 40877879›Full record

Trial reportGenome medicine2025

Integrating breast cancer polygenic risk scores at scale in the WISDOM Study: a national randomized personalized screening trial.

Kirkpatrick B Fergus, Rachel S Heise, Lisa Madlensky, Allison Fiscalini, Leah Sabacan, Sarah Theiner, Shreya Kapoor, Irene A Soto, Amie Blanco, Katherine Ross and 16 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02620852 (Enabling a Paradigm Shift), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02620852 narecruitingnot on this map

Enabling a Paradigm Shift: A Preference-Tolerant RCT of Personalized vs. Annual Screening for Breast Cancer (Wisdom Study)

TypeinterventionalSponsorUniversity of California, San FranciscoRan2016 to 2026Enrolled100,000ConditionsBreast Cancer Screening, Breast Carcinoma in Situ, Breast CancerArmsComplete a health questionnaire, Provide a saliva sample for genetic testing, Screening advice based on a comprehensive risk assessment, Screening advice based on a basic risk assessment
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Polygenic risk scores in clinical applications - opportunities and challenges.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  6. Breast cancer polygenic risk score performance varies by socioeconomic status.medRxiv : the preprint server for health sciences · 2026
    Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Epidemiology, early detection, and management of breast cancer in China: A comprehensive review.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025
    Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Kirkpatrick B FergusDepartment of Surgery, University of California, San Francisco, CA, USA.
Rachel S HeiseDepartment of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA.
Lisa MadlenskyDepartment of Medicine, University of California, San Diego, CA, USA.
Allison FiscaliniDepartment of Surgery, University of California, San Francisco, CA, USA.
Leah SabacanDepartment of Surgery, University of California, San Francisco, CA, USA.
Sarah TheinerDepartment of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA.
Shreya KapoorDepartment of Surgery, University of California, San Francisco, CA, USA.
Irene A SotoDepartment of Surgery, University of California, San Francisco, CA, USA.
Amie BlancoDepartment of Cancer Genetics and Prevention, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Katherine RossDepartment of Cancer Genetics and Prevention, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Deborah Goodman-GruenDepartment of Epidemiology and Biostatistics, University of California, Irvine, CA, USA.
Maren ScheunerDepartment of Medicine, University of California, San Francisco, CA, USA.
Donglei HuDepartment of Medicine, University of California, San Francisco, CA, USA.
Diane HeditsianBreast Oncology Program, Breast Science Advocacy Core, University of California, San Francisco, CA, USA.
Susie BrainBreast Oncology Program, Breast Science Advocacy Core, University of California, San Francisco, CA, USA.
Vignesh A ArasuKaiser Permanente Division of Research, Pleasanton, CA, USA.
Andrea KasterSanford Health, Sioux Falls, SD, USA.
Lisa ChapaDoctors Hospital at Renaissance, Edinburg, TX, USA.
Olufunmilayo I OlopadeCenter for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Martin EklundDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Jeffrey A TiceDepartment of Medicine, University of California, San Francisco, CA, USA.
Elad ZivDepartment of Medicine, University of California, San Francisco, CA, USA.
Laura van 't VeerDepartment of Laboratory Medicine, University of California, San Francisco, CA, USA.
Laura J EssermanDepartment of Surgery, University of California, San Francisco, CA, USA.
Yiwey ShiehDepartment of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. yis4001@med.cornell.edu.
Athena/WISDOM Network Collaborators and Advocate Partners

Funding

Extending the Diversity, Reach, and Generalizability of the WISDOM StudyR01CA237533 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ESSERMAN, LAURA J · 2020 to 2024
$9.1M
Prediction of interval breast cancer risk using genetic variantsK08CA237829 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI SHIEH, YIWEY · 2019 to 2023
$1.3M
ASCO Young Investigator Award 2023YIA- 413 9977333099Breast Cancer Research Foundation SPEC-22-018NCI NIH HHS K08 CA237829NCI NIH HHS K08CA237829NCI NIH HHS R01 CA237533NCI NIH HHS R01CA237533Patient-Centered Outcomes Research Institute PCS-1402-10749U.S. Department of Defense GRANT13922076-BC230196
6 · The paper itself

Abstract

backgroundThe Women Informed to Screen Depending On Measures of risk (WISDOM) Study is the first prospective, population-wide application of personalized breast cancer screening. We aim to demonstrate the feasibility of the study's novel use of polygenic risk scores (PRSs) to tailor screening, evaluate our strategy for adapting PRSs to diverse populations, and quantify the impact of incorporating PRS on the study's screening recommendations.

methodsWISDOM is a randomized, preference-tolerant screening trial in the USA testing the safety and morbidity of risk-based versus annual screening in women aged 40-74 without a prior history of breast cancer. This early report includes participants in the risk-based arm only and compares screening recommendations generated by the Breast Cancer Surveillance Consortium (BCSC) clinical risk model alone versus the BCSC model modified by a PRS (BCSC-PRS). The main outcome of interest is the proportion of participants with a change in screening recommendation after integrating PRS for risk stratification.

resultsIn the risk-based arm, 21,631 participants received a PRS. Small but statistically significant differences in the PRS were seen between major racial and ethnic groups (p < 0.001), and higher PRS was associated with greater extent of family history (p < 0.001) and denser breasts (p < 0.001). BCSC-PRS risk estimates changed the screening recommendations for 14% of women aged 40-49 compared to BCSC alone and for 10% of women aged 50-74. Projected net screening encounters at the population level were similar for both age groups.

conclusionsIn a first-in-kind application of PRS to inform breast cancer screening approaches, we demonstrate feasibility for scaled implementation, moderate changes to individual screening recommendations, and minimal projected downstream burden on the healthcare system.

trial registrationProspectively registered on ClinicalTrials.gov as NCT02620852 on 12/2/2015.

Indexed as

Breast NeoplasmsEarly Detection of CancerMultifactorial InheritancePrecision MedicineAdultAgedFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansMiddle AgedRisk AssessmentRisk FactorsBreast neoplasmsPolygenic risk scoresRisk predictionTranslational genetics

Identifiers

PMID40877879
PMCPMC12395744

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.