The Diagnostic Accuracy of ¹⁸F-FDG PET and ¹⁸F-FES PET for Staging Grade 1–2 Estrogen Receptor–Positive Breast Cancer

Background According to current guidelines, staging of patients with locally advanced breast cancer and local-regional recurrent breast cancer is preferably performed with PET using 2-fluorine 18-fluoro-2-deoxy-d-glucose (¹⁸F-FDG). However, ¹⁸F-FDG PET might underperform in low-grade estrogen receptor (ER)-positive breast cancer. Alternatively, 16α-¹⁸F-fluoro-17β-estradiol (¹⁸F-FES) has emerged as a powerful tracer for in vivo visualization of ER-positive lesions. Purpose To assess whether ¹⁸F-FES PET improves staging of grade 1 or 2 ER-positive breast cancer compared with ¹⁸F-FDG PET. Materials and Methods Patients with clinical stage II/III or local-regional recurrent, grade 1 or 2, ER-positive breast cancer were included between December 2018 and January 2021 in this prospective multicenter pilot study. All participants underwent an ¹⁸F-FES PET examination in addition to standard staging with conventional imaging and ¹⁸F-FDG PET. Both PET scans were independently assessed. The disease stage was determined independently based on conventional imaging and ¹⁸F-FDG PET or ¹⁸F-FES PET. Relevant lesions suspected of malignancy were verified histopathologically, after which a final stage was determined. Results A total of 41 female participants (median age, 56 years [IQR, 48-71 years]) with 44 breast tumors were included. Overall, 29 of 41 participants (71%) were correctly staged at ¹⁸F-FDG PET compared with 34 of 41 (83%) at ¹⁸F-FES PET (<i>P</i> = .18). Seven of 10 and nine of 10 cases of lobular breast cancer were correctly staged at ¹⁸F-FDG and ¹⁸F-FES PET, respectively (70% vs 90%; <i>P</i> = .38) and seven of 12 and 11 of 12 cases of grade 1 tumors, respectively (58% vs 92%; <i>P</i> = .06). Regional lymph nodes were incorrectly staged at ¹⁸F-FDG PET in six of 44 cases (14%), whereas all cases were correctly staged at ¹⁸F-FES PET (<i>P</i> = .02). Both imaging methods had a sensitivity of 100% (95% CI: 59, 100) and a specificity of 91% (95% CI: 76, 98) for the detection of metastatic disease. Conclusion In this prospective pilot study, there was no evidence of a difference in diagnostic accuracy of ¹⁸F-FES PET and ¹⁸F-FDG PET in staging patients with grade 1 or 2 ER-positive breast cancer. Clinical trial registration no. NCT03726931 Published under a CC BY 4.0 license <i>Supplemental material is available for this article.</i> See also the editorial by Fowler in this issue.