Molecular Breast Imaging and Digital Breast Tomosynthesis for Dense Breast Screening: The Density MATTERS Trial.

Background Molecular breast imaging (MBI) relies on the functional uptake of a radiotracer, technetium 99m sestamibi, to reveal cancers that are occult on mammograms due to breast density. Purpose To assess the performance of screening MBI as a supplement to digital breast tomosynthesis (DBT) in women with dense breasts. Materials and Methods In this prospective, multiyear, multicenter trial from five sites, women with dense breasts were prospectively enrolled from 2017 to 2022 and underwent two annual screening rounds of DBT and MBI to assess the incremental cancer detection rate (CDR, reported as cancers per 1000 screenings) of supplemental MBI and to compare other performance metrics of DBT and MBI. Results A total of 2978 participants were included. Participants had a mean age of 56.8 years ± 9.3 (SD) and a mean lifetime Tyrer-Cuzick risk of 12.0% ± 7.9 (SD). At year 1, the CDR was 5.0‰ (15 of 2978 participants) with DBT and 11.8‰ (35 of 2978 participants) with DBT plus prevalence screening MBI (incremental CDR, 6.7‰ [95% CI: 4.2, 10.6]; P < .001); the invasive CDR was 3.0‰ (nine of 2978 participants) with DBT and 7.7‰ (23 of 2978 participants) with DBT plus prevalence screening MBI (invasive incremental CDR, 4.7‰ [95% CI: 2.7, 8.1]; P < .001). At year 2, the CDR was 5.8‰ (15 of 2590 participants) with DBT and 9.3‰ (24 of 2590 participants) with DBT plus incidence screening MBI (incremental CDR, 3.5‰ [95% CI: 1.7, 6.8]; P = .001); the invasive CDR was 1.5‰ (four of 2590 participants) with DBT and 3.9‰ (10 of 2590 participants) with DBT plus incidence screening MBI (invasive incremental CDR, 2.3‰ [95% CI: 0.9, 5.3]; P = .048). The year 1 recall rate was 8.6% (255 of 2978 participants) with DBT and 17.9% (534 of 2978 participants) with DBT plus prevalence screening MBI (difference, 9.4% [95% CI: 8.4, 10.5]). The year 2 recall rate was 8.9% (231 of 2590 participants) with DBT and 13.8% (356 of 2590 participants) with DBT plus incidence screening MBI (difference, 4.8% [95% CI: 4.1, 5.7]). Twenty-nine participants had cancers detected only with MBI: 21 (72%) had invasive cancers (median size, 0.9 cm), 26 (90%) had node-negative cancers, and six (20%) had advanced cancers. The interval cancer rate was 0.7‰ (two of 2978 participants) in year 1 and 0.8‰ (two of 2590 participants) in year 2. Conclusion The addition of MBI to DBT screening increased invasive cancer detection by 2.5-fold and modestly increased the recall rate at the second screening round. © RSNA, 2025 See also the editorial by Fowler in this issue.