The Prevalence and Malignancy Risk of Breast Incidental Uptake Detected by PET/CT with Different Radiopharmaceuticals: An Updated Systematic Review and Meta-Analysis

<b>Background:</b> Meta-analyses on the prevalence and clinical significance of breast incidental uptake (BIU) at PET/CT are available only for [¹⁸F]FDG, showing that BIU is rare but malignant in a substantial proportion of cases. This study aimed to update the pooled prevalence and malignancy risk of BIU using different PET radiotracers, expanding [¹⁸F]FDG-based evidence. <b>Methods:</b> A comprehensive literature search of studies on BIU was carried out in two bibliographic databases, and the literature was screened up to 25 May 2025. Only original articles reporting BIU were selected. A proportion meta-analysis was conducted on a patient-based analysis using a random-effects model to estimate pooled prevalence, malignancy rate, and histological distribution. <b>Results:</b> In total, 29 studies were included in the systematic review and meta-analysis. PET/CT was performed using [¹⁸F]FDG (<i>n</i> = 25), radiolabeled somatostatin analogues (SSAs) (<i>n</i> = 3), or [¹⁸F]fluorocholine (<i>n</i> = 1). The pooled prevalence of BIU was 0.5% for [¹⁸F]FDG PET/CT, 3.4% for SSA PET/CT, and 2.6% for [¹⁸F]fluorocholine. The pooled malignancy rate among BIUs (female patients) was 33.5% for [¹⁸F]FDG, 86.4% for SSA, and 70% for [¹⁸F]fluorocholine PET/CT. Histological data were mainly available for [¹⁸F]FDG PET/CT, showing ductal carcinoma as the most frequent malignant histotype (pooled value 42.2%) and fibroadenoma (pooled value 14.8%) as the most frequent benign histotype. <b>Conclusions:</b> Similar to the case for [¹⁸F]FDG, BIU using other PET radiopharmaceuticals is uncommon but often malignant. Therefore, BIU should prompt dedicated breast imaging and, when indicated, histopathological confirmation. Further well-designed studies are needed to clarify the clinical impact of BIU detection and the prevalence and clinical significance of BIU using tracers other than [¹⁸F]FDG.