Influence of Breast Density and Menopausal Status on Background Parenchymal Enhancement in Contrast-Enhanced Mammography: Insights from a Retrospective Analysis

<b>Background:</b> Contrast-enhanced mammography (CEM) has recently gained recognition as an effective alternative to breast magnetic resonance imaging (MRI) for assessing breast lesions, offering both morphological and functional imaging capabilities. However, the phenomenon of background parenchymal enhancement (BPE) remains a critical consideration, as it can affect the interpretation of images by obscuring or mimicking lesions. While the impact of BPE has been well-documented in MRI, limited data are available regarding the factors influencing BPE in CEM and its relationship with breast cancer (BC) characteristics. <b>Materials:</b> This retrospective study included 116 patients with confirmed invasive BC who underwent CEM prior to biopsy and surgery. Data collected included patient age, breast density, receptor status, tumor grading, and the Ki-67 proliferation index. BPE was evaluated by two radiologists using the 2022 ACR BI-RADS lexicon for CEM. Statistical analyses were conducted to assess the relationship between BPE, patient demographics, and tumor characteristics. <b>Results:</b> The study found a significant association between higher levels of BPE and specific patient characteristics. In particular, increased BPE was more commonly observed in patients with higher breast density (<i>p</i> < 0.001) and those who were pre-menopausal (<i>p</i> = 0.029). Among patients categorized under density level B, the majority exhibited minimal BPE, while those in categories C and D showed progressively higher levels of BPE, indicating a clear trend correlating higher breast density with increased enhancement. Additionally, pre-menopausal patients demonstrated a higher likelihood of moderate to marked BPE compared to post-menopausal patients. Despite these significant associations, the analysis did not reveal a meaningful correlation between BPE intensity and tumor subtypes (<i>p</i> = 0.77) or tumor grade (<i>p</i> = 0.73). The inter-reader agreement for BPE assessment was substantial, as indicated by a weighted kappa of 0.78 (95% CI: 0.68-0.89), demonstrating consistent evaluation between radiologists. <b>Conclusions:</b> These findings suggest that BPE in CEM is influenced by factors like breast density and age, aligning with patterns observed in MRI studies. However, BPE intensity was not associated with tumor subtypes or grades, indicating a poorer prognosis. These insights highlight the potential of BPE as a risk biomarker in preventive follow-up, particularly for patients with high breast density and pre-menopausal status. Further multicentric and prospective studies are needed to validate these results and deepen the understanding of BPE's role in CEM diagnostics.