Contrast-Enhanced Mammography for Breast Cancer Screening: A Systematic Review and Meta-Analysis.

OBJECTIVE

To evaluate pathway-specific cancer detection and summarise screening outcomes (recall/biopsy/PPV3) for contrast-enhanced mammography when reported, and to compare them with those for low-energy mammography and breast MRI.

METHODS

This systematic review and meta-analysis followed PRISMA guidelines. PubMed (MEDLINE), Embase, Scopus, and Web of Science were searched from January 1, 2011, through August 31, 2025, for studies evaluating contrast-enhanced mammography in screening or surveillance populations (including supplemental/add-on screening and surveillance of patients with a personal history of breast cancer). Diagnostic, recall, and problem-solving studies were excluded. Screening pathways were categorized as: (1) direct comparison with low-energy mammography, (2) direct comparison with MRI, and (3) add-on CEM to mammography-based screening. Random-effects meta-analyses were performed when designs were comparable. Comparisons between CEM and MRI were summarized qualitatively because of heterogeneity and limited cancer events across studies. Single-arm screening studies were summarized descriptively. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2).

RESULTS

Fourteen studies met eligibility criteria for qualitative synthesis; seven screening and surveillance studies contributed to the meta-analysis. Compared with low-energy mammography, CEM detected 9.3 additional cancers per 1,000 women screened (risk difference [RD], +9.3 per 1,000; 95% CI, 4.0-14.6; P < 0.01; I2 = 0%). Three studies directly compared CEM with MRI in screening settings and were summarized qualitatively because of heterogeneity and limited cancer events.

CONCLUSION

In screening and surveillance populations, contrast-enhanced mammography increases cancer detection compared with low-energy mammography. Evidence from available comparative studies suggests that cancer detection with CEM may be broadly comparable to MRI in selected screening contexts; however, the limited number of studies and heterogeneous designs preclude definitive comparative conclusions. These pathway-specific estimates may inform clinical implementation and the design of prospective screening trials.