Supplemental Breast Ultrasound in Mammography Screening for Women with Critically Dense Breasts

Background: The sensitivity of mammography screening is compromised in women with dense breast tissue. Supplemental ultrasound (S-US) can enhance cancer detection, but evidence regarding its feasibility, harms, and benefits within Western population-based screening programs remains limited. Methods: This pragmatic, prospective controlled trial was integrated into the German national mammography screening program across 16 sites. Breast density was assessed using automated AI software. Women with "critically dense" breasts (top 15-20%) were offered handheld supplemental S-US in addition to mammography (MXUS). The control group (MX-only) comprised women with comparable densities who did not receive S-US. Primary outcomes included cancer detection rate (CDR), recall rate, biopsy rate, and short-term follow-up recommendations. Results: From May 2020 to March 2024, 25,341 women underwent MXUS, while 38,529 received MX-only. The CDR was significantly higher in the MXUS group, at 10.7 per 1000 (95% CI: 9.4-12.0) compared to 7.2 per 1000 (95% CI: 6.4-8.1) in the MX-only group, yielding an incremental CDR of 3.5 per 1000 (95% CI: 1.9-5.0). However, MXUS led to higher rates of recall (6.6% vs. 5.4%), biopsies (3.2% vs. 1.5%), and short-term follow-up recommendations (0.9% vs. 0.5%). Conclusions: Implementing quality-assured S-US for women with critically dense breasts substantially increases the detection of invasive cancers, but also raises false positives. While these results support density-adapted screening, the high resource intensity suggests that future strategies should optimize risk stratification to target S-US more selectively. Long-term data are required to confirm clinical benefits.