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

: 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. : 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. : CEM showed higher sensitivity than LE-CEM (83.0% vs. 68.9%, < 0.001) with similar specificity (90.8% vs. 92.5%, = 0.176). Mean AUC increased from 0.856 for LE-CEM to 0.936 for CEM ( < 0.001). CEM and MRI showed comparable sensitivity (82.9% vs. 86.1%, = 0.547), specificity (90.8% vs. 86.5%, = 0.318), and mean AUC (0.936 vs. 0.933; = 0.839), confirming noninferiority of CEM. MGD per view ranged from 1.56 to 3.10 mGy. : 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.