WISDOM Trial: Shaping the Future of Breast Cancer Screening

The WISDOM trial showed that risk-based screening reduced occurrences of late-stage (≥IIB) screen-detected breast cancers compared with annual mammography while preserving overall cancer detection.

Randomized allocation of 28,372 women aged 40–74 compared a multicomponent, stratified algorithm to usual annual mammography, with coprimary endpoints of stage ≥IIB screen-detected cancers and biopsy frequency/noninferiority for overall cancer detection. Notably, risk-based screening yielded fewer stage ≥IIB screen-detected cancers (21 vs 31 events; 30.0 vs 48.0 per 100,000 person‑years) and met the prespecified noninferiority threshold for overall cancer detection. Rather than longer intervals inevitably increasing late-stage diagnoses, interval tailoring by risk reduced later-stage presentations.

The principal diagnostic trade-offs were higher biopsy rates and greater MRI use concentrated in higher-risk categories under the risk-based protocol. Quantitatively, the biopsy rate difference was 98.7 per 100,000 person‑years; mammography use declined by 3,835.9 per 100,000 person‑years; and MRI utilization rose, particularly among the highest and elevated risk groups.

Adherence deviations were common—many participants screened more often than assigned—narrowing the separation between strategies and affecting real-world impact.