Which clinical, radiological, histological, and molecular parameters are associated with the absence of enhancement of known breast cancers with Contrast Enhanced Digital Mammography (CEDM)?

BACKGROUND: CEDM has demonstrated a diagnostic performance similar to MRI and could have similar limitations in breast cancer (BC) detection. PURPOSE: The aim of our study was to systematically analyze the characteristics of the lesions with the absence of enhancement with CEDMs, called false-negatives (FNs), in order to identify which clinical, radiological, histological and molecular parameters are associated with the absence of enhancement of known BCs with CEDMs, and which types of BC are most likely to cause FNs in CEDMs. We also tried to evaluate which parameters instead increased the probability of showing enhancement in the same context. MATERIALS AND METHODS: Included in our study group were 348 women with 348 diagnosed BCs performing CEDM as preoperative staging. Two breast-imaging radiologists reviewed the CEDM exams. The absence of perceptible contrast enhancement at the index cancer site was indicative of an FN CEDM, whereas cases with appreciable enhancement were considered true positives (TPs). Dichotomic variables were analyzed with Fisher's exact probability test or, when applicable, the chi-square test. Binary logistic regression was performed on variables shown to be significant by the univariate analysis in order to assess the relationship between predictors (independent variables) and TFNs (outcome). RESULTS: Enhancement was observed in 317 (91.1%) of the 348 BCs. From the 31 (8.9%) lesions which were FNs, we excluded 12 (38.7%) which showed an artifact generated by the post biopsy hematoma and 6 (19.4%) which were outside the CEDM field of vision. We thus obtained 13 (41.9%) BCs considered "True False Negatives" (TFNs), i.e. BCs which showed no enhancement despite being within the CEDM field of vision and failed to show post biopsy hematoma artifacts. We found that the TFNs frequently have a unifocal disease extension, diameter <10 mm, a lower number of luminal B HER2-subtypes, a higher number of DCIS, and an index lesion with microcalcifications. CONCLUSIONS: The parameters we found to be associated with no enhancement of known BCs with CEDMs were: unifocal disease extension, DCIS histotype, lesion dimensions <10 mm, and index lesion with microcalcifications. The characteristics that instead increase the probability of showing enhancement were US mass, Luminal B HER2 negative molecular subtype, the presence of an invasive ductal component, and lesion dimensions ≥10 mm.