Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial

2016/11/01 by Yiwey Shieh, Martin Eklund, Lisa Madlensky +8 · 252 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #BRCA gene mutations in cancer #Bioinformatics #Breast cancer #Breast cancer screening #Cancer #Cancer screening #Clinical trial #Colorectal Cancer Screening and Detection #Computer science #Environmental health #Family medicine #Global Cancer Incidence and Screening #Internal medicine #Mammography #Medical physics #Medicine #Pathology #Penetrance #Personalized medicine #Population #Precision medicine #Randomized controlled trial #Risk assessment

paper · pdf · doi:10.1093/jnci/djw290

published in JNCI Journal of the National Cancer Institute 109(5), djw290 (Oxford University Press)

openalex publication_date 2016/11/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30

Abstract

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.

Citations

• American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography
• Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers

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• The WISDOM Study: breaking the deadlock in the breast cancer screening debate. [europepmc]
• Determining Risk of Barrett's Esophagus and Esophageal Adenocarcinoma Based on Epidemiologic Factors and Genetic Variants. [europepmc]
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• Risk, Prediction and Prevention of Hereditary Breast Cancer - Large-Scale Genomic Studies in Times of Big and Smart Data. [europepmc]
• Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. [europepmc]
• Cancer prevention and screening: the next step in the era of precision medicine. [europepmc]
• Genome-wide association studies and polygenic risk scores for skin cancer: clinically useful yet? [europepmc]
• A Polygenic Risk Score for Breast Cancer in US Latinas and Latin American Women. [europepmc]
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• Clinical applications of polygenic breast cancer risk: a critical review and perspectives of an emerging field. [europepmc]
• Personalized early detection and prevention of breast cancer: ENVISION consensus statement. [europepmc]
• Practicing precision medicine with intelligently integrative clinical and multi-omics data analysis. [europepmc]
• Advanced Breast Cancer Definitions by Staging System Examined in the Breast Cancer Surveillance Consortium. [europepmc]
• Pan-cancer analysis demonstrates that integrating polygenic risk scores with modifiable risk factors improves risk prediction. [europepmc]
• Women's Views on Multifactorial Breast Cancer Risk Assessment and Risk-Stratified Screening: A Population-Based Survey from Four Provinces in Canada. [europepmc]
• Prospective Evaluation of the Addition of Polygenic Risk Scores to Breast Cancer Risk Models. [europepmc]
• Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation (PERSPECTIVE I&I). [europepmc]
• Fully Automated Volumetric Breast Density Estimation from Digital Breast Tomosynthesis. [europepmc]
• The current status of risk-stratified breast screening. [europepmc]
• BREAst screening Tailored for HEr (BREATHE)-A study protocol on personalised risk-based breast cancer screening programme. [europepmc]
• Development of a clinical polygenic risk score assay and reporting workflow. [europepmc]
• Breast Cancer in Asia: Incidence, Mortality, Early Detection, Mammography Programs, and Risk-Based Screening Initiatives. [europepmc]
• Incorporating Alternative Polygenic Risk Scores into the BOADICEA Breast Cancer Risk Prediction Model. [europepmc]
• Recent Trends in Biosensing and Diagnostic Methods for Novel Cancer Biomarkers. [europepmc]

Related

• Breast Cancer Screening for Women at Average Risk
• A Systematic Assessment of Benefits and Risks to Guide Breast Cancer Screening Decisions
• OR Forum—A POMDP Approach to Personalize Mammography Screening Decisions
• Practice Bulletin Number 179: Breast Cancer Risk Assessment and Screening in Average-Risk Women
• Screening Mammography for Women 40 to 49 Years of Age: A Clinical Practice Guideline from the American College of Physicians