Non-inferiority Study of Contrast-enhanced Digital Mammography (CEDM) vs Magnetic Resonance Imaging (MRI) in Terms of Diagnostic Accuracy in Patients Undergoing Preoperative Staging of Established Invasive Breast Cancer

This is a monocentric, prospective, experimental non-inferiority study evaluating the diagnostic performance of Contrast-Enhanced Digital Mammography (CEDM/CEM) compared to Breast Magnetic Resonance Imaging (MRI) in the preoperative assessment and staging of breast cancer.

MRI, recognized for its high sensitivity and three-dimensional visualization capabilities without ionizing radiation, is often used in specialized centers for detailed staging. However, it suffers from practical limitations including high cost, long exam duration (~7-10 minutes), and cost-effective. Preliminary studies suggest its diagnostic accuracy may be comparable to, or even better than, MRI, especially regarding specificity and lesion size estimation. Furthermore, CEM can be used in patients with contraindications to MRI, including those with pacemakers, cochlear implants, or severe claustrophobia.

The study will enroll approximately 216 patients up to December 2025, divided in tho groups: 108 patients with already confirmed invasive breast cancer undergoing preoperative staging; 108 patients scheduled for neoadjuvant chemotherapy followed by surgery.

CEM and MRI will be performed for all enrolled participants. Histological examination of biopsy or surgical specimens will serve as the reference standard for evaluating diagnostic performance.

The primary outcome is to determine diagnostic accuracy (including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) of CEDM versus MRI, using histopathology as the gold standard. A non-inferiority margin (Δ) of 15% is defined. The non-inferiority hypothesis will be tested using paired binary outcomes, and sample size calculations for groups 1 and 2, accounting for dependent diagnostic testing.

The secondary endpoint are:

• evaluating interobserver agreement between radiologists interpreting CEDM (Cohen's kappa and intraclass correlation coefficients).
• comparison of lesion size estimations and regression evaluations in patients undergoing neoadjuvant chemotherapy at baseline (T0), 3 months (T3), and 6 months (T6).

Descriptive statistics will summarize demographic and clinical characteristics. For hypothesis testing, paired comparisons will be used: Student's t-test or Wilcoxon test for continuous variables; McNemar test or Fisher's exact test for categorical variables. Pearson correlation coefficients will assess the relationship between imaging measurements and histology. Diagnostic accuracy comparisons will assess the lower bound of the 95% confidence interval against the non-inferiority threshold.

Participants must be women over 30 years of age with a BI-RADS mammographic pattern >1, scheduled for a diagnostic MRI and meeting one of the five group classifications. Key exclusion criteria include: breast implants, known BRCA1 or BRCA2 mutations, contraindications to MRI, or impaired renal function (eGFR <30 mL/min). All participants must provide informed consent.

Participants will undergo a routine clinical MRI followed by CEDM during a scheduled visit. Imaging will be interpreted independently by two radiologists, blinded to each other's findings, with subsequent consensus reporting. Pseudonymized data will be recorded, including imaging findings, histological results, and any adverse reactions to contrast agents.

In group 2 (neoadjuvant chemotherapy), patients will also undergo interim imaging with both MRI and CEDM at 3 and 6 months to assess treatment response.