Clinical Performance of Contrast-Enhanced Mammography Versus Breast MRI in Women at Increased Breast Cancer Risk

<b>Background/Objectives</b>: Surveillance of women at increased risk for breast cancer requires high-sensitivity imaging. This study compared contrast-enhanced mammography (CEM) with low-energy CEM (LE-CEM) and breast MRI in this population. <b>Methods</b>: This retrospective analysis included 461 women enrolled in a high-risk imaging protocol (March 2019-October 2022). Lifetime breast cancer risk was estimated using the Tyrer-Cuzick model. All participants underwent CEM and breast MRI ≥ 72 h apart. LE-CEM images were used as a surrogate for digital mammography. Four readers independently interpreted LE-CEM and CEM; a separate group of four readers interpreted MRI. Diagnostic performance was assessed using sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) within a multireader, multicase framework. Noninferiority testing was performed with Δ = 0.05. Mean glandular dose (MGD) for CEM was recorded. <b>Results</b>: CEM showed higher sensitivity than LE-CEM (83.0% vs. 68.9%, <i>p</i> < 0.001) with similar specificity (90.8% vs. 92.5%, <i>p</i> = 0.176). Mean AUC increased from 0.856 for LE-CEM to 0.936 for CEM (<i>p</i> < 0.001). CEM and MRI showed comparable sensitivity (82.9% vs. 86.1%, <i>p</i> = 0.547), specificity (90.8% vs. 86.5%, <i>p</i> = 0.318), and mean AUC (0.936 vs. 0.933; <i>p</i> = 0.839), confirming noninferiority of CEM. MGD per view ranged from 1.56 to 3.10 mGy. <b>Conclusions</b>: Contrast-enhanced mammography provides diagnostic accuracy equivalent to breast MRI and superior to LE-CEM, with acceptable radiation dose, supporting its use for surveillance in women at increased breast cancer risk.