Contrast-enhanced mammography (CEM) combines the strengths of digital mammography with the use of intravenous contrast agents, enhancing breast imaging capabilities (Covington et al., 2024; Neeter et al., 2021; Sogani et al., 2021). Both CEM and contrast-enhanced magnetic resonance imaging (CE-MRI) highlight areas of neo-angiogenesis in malignant lesions, providing functional imaging that offers superior sensitivity and specificity compared to purely anatomical techniques such as standard mammograms or ultrasound (US) (Covington et al., 2024; Lorente-Ramos et al., 2023). However, CE-MRI has several limitations, including a high false-positive rate, the need for specialized breast coils, and significant costs. Moreover, it is not suitable for patients with severe claustrophobia, morbid obesity (due to weight restrictions), or those with pacemakers or metallic implants. CEM, on the other hand, serves as a more patient-friendly and cost-effective alternative, offering faster imaging and interpretation times (Covington et al., 2024; Neeter et al., 2021; Sogani et al., 2021). Both modalities identify early, subtle lesions that are difficult to detect and biopsy with conventional methods. Until recently, the only way to biopsy contrast-enhanced findings was through an MR-guided approach, which presents the same limitations as MRI (costs, limited availability, and long procedure times). Recently, CEM-guided biopsy has been introduced as a faster and more cost-effective alternative, with the main advantage of being performed within the breast diagnostic unit (Alcantara et al., 2022; Aribal et al., 2024; James, 2022; Tang & Cheung, 2023).

Currently, the evidence on the usefulness of CEM is still limited, particularly concerning its clinical indications. Indeed, considering the non-specific features of “contrast-enhanced only” findings (e.g., areas of healthy parenchyma showing significant enhancement due to hormonal factors),a considerable risk of performing unnecessary biopsies exists. While in some cases CEM-guided biopsy may be justified by patient's clinical history (e.g., a patient with ongoing breast cancer and suspected multifocal or multicentric disease), in patients who do not have particular risk factors the likelihood of an unnecessary CEM-guided biopsy may be higher.

The purpose of this study is to identify clinical and/or radiological factors predictive of malignancy of contrast-enhanced only findings undergoing contrast-enhanced mammography (CEM)-guided biopsy, to better identify patients who could benefit from this procedure and avoiding it in cases with a low probability of malignancy.