Background Parenchymal Enhancement on Contrast-Enhanced Mammography: Determinants, Technical Considerations, and Emerging Role as a Breast Cancer Risk Biomarker

Background/Objectives: Background parenchymal enhancement (BPE) on contrast-enhanced mammography (CEM) represents enhancement of otherwise normal fibroglandular tissue. Although BPE is well established in breast MRI interpretation, its determinants, technical variability, diagnostic implications, and potential value as a breast cancer risk biomarker on CEM remain incompletely defined. This review summarizes the current evidence and outlines the steps required for responsible clinical translation. Methods: PubMed/MEDLINE was searched from database inception through April 2026 using terms related to CEM and BPE. Reference lists of eligible studies and relevant reviews were also screened. Human studies evaluating CEM-specific BPE in relation to biologic or hormonal determinants, breast density, technical factors, measurement methods, reproducibility, diagnostic performance, temporal variability, asymmetry, or breast cancer outcomes were synthesized narratively. Results: CEM BPE is influenced by age, menopausal status, menstrual and hormonal factors, lactation, endocrine therapy, breast density, contrast timing, view order, compression, positioning, imaging system, and post-processing. Because CEM is a projection-based technique acquired over several minutes, its BPE should not be considered physiologically interchangeable with MRI BPE. Moderate or marked BPE may reduce lesion conspicuity or mimic abnormal enhancement, particularly when asymmetric. Early studies suggest that higher CEM BPE may be associated with prevalent or subsequent breast cancer after adjustment for established risk factors, but findings remain heterogeneous and derive predominantly from retrospective, single-center cohorts. Quantitative and artificial-intelligence approaches are promising but require technical normalization, reproducibility testing, multicenter validation, and linkage to clinically meaningful outcomes. Conclusions: CEM BPE is a functional imaging feature shaped by patient biology, tissue composition, acquisition technique, and reader assessment. It should currently be reported and interpreted in context but should not independently alter screening, biopsy, or risk-management decisions. Translation into a clinically useful biomarker will require standardized measurement, longitudinal prognostic validation, demonstration of added value beyond established risk models, and prospective evidence that BPE-informed care improves outcomes without producing excessive harms or costs.