Meta-analysis of prospective studies evaluating breast cancer detection and interval cancer rates for digital breast tomosynthesis versus mammography population screening

Introduction: Breast cancer (BC) screening using digital breast tomosynthesis (DBT) has been shown to increase cancer detection compared with mammography; however, it is unknown whether DBT impacts interval cancer rate (ICR). Methods: We systematically identified prospective DBT studies reporting data on screen-detected and interval BCs to perform a study-level meta-analysis of the comparative effect of DBT on ICR in population screening. Meta-analysis of cancer detection rate (CDR), ICR, and the differences between DBT and mammography in CDR and ICR pooled estimates, included random-effects. Sensitivity analysis examined whether study methods (imaging used, comparison group design, interval BC ascertainment) affected pooled estimates. Results: Five eligible prospective (non-randomised) studies of DBT population screening reported on 129,969 DBT-screened participants and 227,882 mammography-only screens, including follow-up publications reporting interval BC data. Pooled CDR was 9.03/1000 (95% confidence interval [CI] 8.53-9.56) for DBT, and 5.95/1000 (95% CI 5.65-6.28) for mammography: the pooled difference in CDR was 3.15/1000 (95% CI 2.53-3.77), and was evident for the detection of invasive and in-situ malignancy. Pooled ICR was 1.56/1000 DBT screens (95% CI 1.22-2.00), and 1.75/1000 mammography screens (95% CI 1.46-2.11): the estimated pooled difference in ICR was -0.15/1000 (95% CI -0.59 to 0.29) and was not substantially altered in several sensitivity analyses. Conclusions: Meta-analysis shows consistent evidence that DBT significantly increased CDR compared with mammography screening; however, there was little difference between DBT and mammography in pooled ICR. This could suggest, but does not demonstrate, some over-detection. Meta-analysis using individual participant data, randomised trials and comparative studies quantifying cumulative detection and ICR over repeat DBT screen-rounds would provide valuable evidence to inform screening programs.