Is mammography screening based on patient risk ready to take over for age-based screening? Results from the WISDOM study presented at last week’s San Antonio Breast Cancer Symposium and published simultaneously in JAMA suggest that while risk-based screening has its merits, more work may need to be done.
Cancer screening exams like mammography have reduced disease-specific mortality, but (with the exception of lung cancer screening) all use exclusively age-based criteria to determine who should get screened.
- Age isn’t a great tool for determining who’s at higher risk of getting cancer, but it’s the best tool we’ve had – up to now.
New cancer risk prediction tools are now becoming available, prompting debate over whether these techniques could make screening more precise by directing it to those most at risk.
- Higher-risk people could get more frequent screening, while lower-risk individuals might be directed to longer screening intervals.
The WISDOM study presented at SABCS 2025 investigates this question. WISDOM is a randomized clinical trial that compared risk-based breast screening to age-based annual screening in 28.4k women followed for five years.
- Risk categorization was performed with genetic testing, polygenic risk scores, and BCSC scores, which incorporate family history and imaging results.
Women in the risk-based screening group were directed into one of four screening strategies, from alternating mammography and MRI every six months for high-risk women to no screening until age 50 for low-risk women.
- The study’s primary outcomes were detection rates for breast cancers rated as stage IIB or higher and effectiveness in reducing biopsy rates – a proxy for screening-caused morbidity.
Across the study population, researchers found…
- The rate of mammograms per 100k person-years was lower in the risk-based cohort compared to age-based screening (43.1k vs. 46.9k).
- The rate of stage IIB or higher cancers per 100k person-years was also lower in the risk-based cohort (30 vs. 48).
- But there was no statistically significant difference in biopsy rates, with a rate difference of 99 per 100k person-years (p = 0.10).
One problem with the WISDOM trial was that the actual screening exams were performed outside the study, and some patients did not comply with screening recommendations, potentially confounding results.
The Takeaway
The WISDOM authors concluded that a risk-based screening approach is safe, but the lack of a difference in biopsy rates makes one wonder if veering from established age-based criteria is worth it. In any event, the coming arrival of risk stratification based on AI mammogram analysis could make the genetic testing-based approach used in WISDOM obsolete.
