CONTRAST ENHANCED MAMMOGRAPHY IN WOMEN WITH PREVIOUS BREAST CANCER OPERATED WITH CONSERVING SURGERY (COMBO TRIAL): A PROSPECTIVE INTRA-INDIVIDUAL STUDY

PURPOSE Women with Personal History of Breast Cancer (PHBC) face a higher risk of recurrence or new primary disease. The aim of this study was to present the results of the 'COMBO TRIAL,' a prospective intra-individual study evaluating the performance of Contrast- Enhanced Mammography (CEM) compared with Digital Mammography (DM) in the surveillance of women with PHBC. MATERIAL AND METHODS Between January 2023 and February 2025, 1551 asymptomatic women who underwent breast-conserving surgery within the previous 10 years were invited to undergo CEM instead of DM for routine surveillance. Exclusion criteria comprised suspicious symptoms of breast cancer, history of allergy to iodinated contrast agents, renal impairment and the presence of breast implants. For each patient, one radiologist interpreted CEM (Low energy [LE] + recombined images), while a second independent, blinded radiologist evaluated only LE images (equivalent to DM). Both readers assigned independent BI-RADS scores according to the ACR BI-RADS® and the CEM Supplement. The reference standard was 1-year follow-up for negative cases (BI-RADS 1-2) and histopathology for cases rated BI-RADS 4 and 5. Primary endpoints included the cancer detection rate (CDR) of DM and CEM, and the incremental CDR (iCDR) of CEM. Secondary endpoints included recurrence rate, recall rate, sensitivity, specificity, positive predictive value (PPV1 and PPV3), negative predictive value (NPV), overall accuracy, and adverse reaction rate. Diagnostic performance differences were tested using McNemar’s and Chi squared tests (p < 0.05 significant). RESULTS Of 969 women enrolled, 936 (mean age ± SD; 58.2 ±10.2) were included in the analysis. A total of 79 women were recalled, for an overall recall rate of 8.4%. Twenty-seven breast cancers were detected: 16 (11 invasive + 5 Ductal Carcinoma In Situ [DCIS]) by both DM and CEM, while CEM identified 11 additional cancers (10 invasive + 1 DCIS). Three cancers were missed by both DM and CEM but detected at subsequent ultrasound, resulting in a recurrence rate of 3.2%. The CDR was 28.9 per 1000 for CEM and 17.1 per 1000 for DM, yielding an iCDR of 11.8 per 1000 (p=0.001). Compared with DM, CEM showed higher sensitivity (90.0% [95% CI: 73.5-97.9] vs 53.3% [95% CI: 34.3-71.7] p=0.001), slightly lower specificity (95.3% [95% CI: 93.7-96.5] vs 97.9% [95% CI: 96.7- 98.7] p<0.001); similar PPV1 (38.6% [95% CI: 27.2-50.9] vs 45.7% [95% CI: 28.8-63.4]) and PPV3 (55.1% [95% CI: 40.2-69.3] vs 57.1% [95% CI: 37.2-75.6]), higher NPV (99.7% [95% CI: 98.9-99.9] vs 98.5% [95% CI: 97.4-99.2] p=0.013), and higher overall accuracy (0.93 vs 0.76; p<0.001). The rate of adverse reaction to contrast was 0.74%, all mild or moderate. CONCLUSION The results of the COMBO trial show that implementing CEM in the surveillance of women with PHBC significantly increases the cancer detection rate, particularly for early invasive cancers. Final outcomes, including interval cancers assessment, are awaited to provide a comprehensive evaluation.