**1. Introduction**

18F-FDG PET/CT is a very useful imaging tool in staging breast cancer (BC) patients with locally advanced disease [1–3] or in restaging patients with biochemical relapse without evidence of structural recurrence on conventional imaging procedures [4,5]. However, the 18F-FDG avidity of BC is associated with histopathological features and can thus show relevant variations [6,7]. In particular, patients with less differentiated, triple-negative BC often present with 18F-FDG avid metastases and, in this setting, 18F-FDG PET/CT can provide relevant additional information when compared with morphological imaging modalities or with surgical staging [8]. Conversely, well-differentiated and oestrogen receptor-positive (ER+) BCs often present metastases with relatively low glucose consumption and thus inconstant positivity on 18F-FDG PET/CT. Therefore, in this particular field of patients, more specific PET/CT agents, such as receptor tracers, still represent an unmet diagnostic need.

**Citation:** Piccardo, A.; Fiz, F.; Treglia, G.; Bottoni, G.; Trimboli, P. Head-to-Head Comparison between 18F-FES PET/CT and 18F-FDG PET/CT in Oestrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-Analysis. *J. Clin. Med.* **2022**, *11*, 1919. https://doi.org/ 10.3390/jcm11071919

Academic Editors: Arutselvan Natarajan and Moritz Wildgruber

Received: 11 February 2022 Accepted: 28 March 2022 Published: 30 March 2022

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Fluorine-oestradiol 18F-FES PET/CT has been introduced as an effective imaging procedure in patients with metastatic BC and previous histological confirmation of ER+ status on the primary tumour, to assess whether ERs are also expressed in loco-regional or distant metastases [9]. Indeed, 18F-FES PET/CT provides excellent whole-body information about heterogeneity in ER expression in BC metastases, thus allowing to predict the response to endocrine therapy [10]. However, little can be said about the diagnostic role of this receptor-specific tracer and, although some studies proved its low sensitivity in detecting BC liver metastases [11,12], others showed its relevant diagnostic impact on BC bone metastases [11,13]. Overall, it is not clear yet whether 18F-FES PET/CT could be proposed as a core imaging procedure in ER+ BC patients with suspected distant metastases and whether it could be preferred to 18F-FDG PET/CT, at least in some specific instances.

To clarify this diagnostic issue, we performed a systematic search of the literature to identify original studies reporting a diagnostic head-to-head comparison of 18F-FES PET/CT and 18F-FDG PET/CT in detecting ER+ BC metastases. We also carried out a meta-analysis of the available data using sensitivity as a diagnostic outcome measure.

### **2. Materials and Methods**

The systematic review was conducted according with the PRISMA statement [14].
