BACKGROUND AND PURPOSE:

• Esserman et al. (JAMA, 2025) investigated whether risk-based breast cancer screening is a feasible alternative to annual mammography

METHODS:

• Parallel-group, pragmatic, multicenter randomized clinical trial
  • Women Informed to Screen Depending on Measures of Risk (WISDOM) trial 
  • Women from all 50 US states
• Participants
  • 40 to 74 years
  • Without
    • Prior diagnoses of breast cancer
    • Ductal carcinoma in situ
    • Prophylactic bilateral mastectomy
  • Women who declined randomization were enrolled in an observational cohort
• Interventions
  • Risk-based screening based on the following
    • Sequencing of 9 breast cancer susceptibility genes | Polygenic risk score | The Breast Cancer Surveillance Consortium (v2) risk prediction tool
    • Highest risk
      • ≥6% 5-year risk | High-penetrance pathogenic variant
      • Strategy: alternating mammography and MRI every 6 months and counseling
    • Elevated risk
      • Top 2.5 risk percentile by age
      • Strategy: Annual mammography and risk-reduction counseling
    • Average risk
      • Strategy: Biennial mammography
    • Low risk
      • Aged 40 to 49 years and <1.3% 5-year risk
      • Strategy: No screening until risk is ≥1.3%, or age 50
  • Annual screening with mammography
• Primary outcomes
  • Noninferiority for stage ≥IIB cancers
  • Superiority for reducing biopsy rates
• Secondary outcomes
  • Identification of stage ≥IIA cancers
  • Mammogram rates
  • Uptake of prevention strategies in higher risk cohorts
  • Preference for screening group in the observational cohort
  • Ductal carcinoma in situ
  • MRI
  • Stage-specific cancer rates

RESULTS:

• 28,372 women
  • Mean age: 54 (SD, 9.6) | Non-Hispanic White: 77%
  • Median follow-up: 5.1 years
• The rate of stage ≥IIB cancers was noninferior in the risk-based compared with the annual group
  • Risk-based: 30.0 (95% CI, 16.3 to 43.8) per 100,000 person-years
  • Annual: 48.0 (95% CI, 30.1 to 65.5) per 100,000 person-years
  • Rate difference (RD) −18.0 per 100,000 person-years (95% CI, −40.2 to 4.1)
• The rate of breast biopsies was not lower in the risk-based group
  • RD 98.7 per 100,000 person-years (95% CI, −17.9 to 215.3)
• This was despite fewer mammograms in the risk-based group
  • RD 3835.9 (95% CI, −4516.8 to −3154.9)
• As risk category increased, so did the cumulative incidence of
  • Cancer
  • Biopsy
  • Mammogram
  • MRI
• In the observational cohort, the majority of participants chose risk-based screening: 89%

CONCLUSION:

• A risk-based breast cancer screening approach did not lead to safety concerns (higher rates of later stage disease) nor reduce the number of biopsies performed
• The authors state

The WISDOM study demonstrated that a risk-based approach successfully stratifies the population for breast cancer risk and is safe and acceptable to women

Work is ongoing in the next platform iteration, WISDOM 2.0, to utilize PRS for subtype-specific and ancestry-based risk assessment, along with radiographic (AI) measures of risk

Learn More – Primary Sources:

Risk-Based vs Annual Breast Cancer Screening: The WISDOM Randomized Clinical Trial