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

Clinical Snapshot

Key Findings

• P Value: P < 0.01

• Effect Size: Risk difference of +9.3 additional cancers per 1,000 women screened with CEM versus low-energy mammography

• Primary Outcome: Cancer detection rate of CEM compared with low-energy mammography in screening and surveillance populations

• Nnt Or Sensitivity: Number needed to screen (NNS) to detect one additional cancer with CEM over LEM: approximately 108 women (derived from RD of 9.3/1,000); I² = 0% across 7 contributing studies. CEM vs. MRI comparison: qualitative synthesis only — three studies suggest broadly comparable detection, but definitive conclusions are not possible.

• Confidence Interval: 95% CI: 4.0 to 14.6 additional cancers per 1,000 women screened

Clinical Application

CEM requires intravenous iodinated contrast administration, which introduces procedural complexity, cost, and risk of contrast reactions compared with standard mammography. It requires modified mammography equipment capable of dual-energy acquisition, which is increasingly available in tertiary and some secondary centres. Workflow integration, patient selection protocols, and radiologist training are prerequisite implementation considerations. The technique is more accessible and less claustrophobia-inducing than MRI, and generally less expensive, which may favour adoption in resource-constrained settings. In Australia, breast cancer screening is delivered through BreastScreen Australia, which currently funds standard digital mammography for women aged 40–74 years. CEM is not currently listed on the Medicare Benefits Schedule (MBS) as a screening modality, and is not a TGA-mandated standard of care for screening. Breast MRI is MBS-funded for high-risk surveillance (Item 63464) in women with BRCA1/2 mutations or equivalent lifetime risk ≥25%. CEM could represent a cost-effective bridge for women who meet MRI surveillance criteria but have contraindications (e.g., pacemakers, severe claustrophobia) or for whom MRI access is limited in regional and rural Australia. RACGP and the Royal Australian and New Zealand College of Radiologists (RANZCR) have not yet issued formal guidance on CEM for population screening. The findings of this review support the case for prospective Australian trials and MBS consideration, but are insufficient to justify immediate policy change. Iodinated contrast agents used in CEM are TGA-registered; contrast-induced adverse event protocols are well-established in Australian radiology departments. Women undergoing breast cancer screening or surveillance, particularly those in whom standard mammography has limited sensitivity (e.g., dense breast tissue, elevated lifetime risk, personal history of breast cancer). The incremental detection benefit is most likely to be clinically meaningful in intermediate-to-high risk populations where MRI is indicated but access or tolerability is limited.

Abstract

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.

References

1. 1.Saluja, K. V., Saxena, S., Khokhar, H., Sharma, A. K., Meena, D., Sharma, A., & Goyal, M. (2026). Contrast-enhanced mammography for breast cancer screening: A systematic review and meta-analysis. Journal of Breast Imaging. Advance online publication. https://doi.org/10.1093/jbi/wbag025