NCT03726931: FORESIGHT

FES (16α-[18F]-Fluoro-17β-estradiol)-PET: Towards a New Standard to Stage Locally Advanced and Recurrent, Estrogen Receptor Positive (ER+) Breast Cancer? Pilot Study to Compare [18F]FES-PET and [18F]FDG-PET

Completed NA Last updated 3 May 2023

What this trial tests

NA trial testing 18F-Fluorestradiol PET/CT scan in Breast Cancer in 40 participants. Completed in 29 January 2023.

Timeline

13 November 2018

Primary endpoint
29 January 2023

29 January 2023

Quick facts

Lead sponsor	Amsterdam UMC, location VUmc
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	40
Start date	13 November 2018
Primary completion	29 January 2023
Estimated completion	29 January 2023
Sites	1 location across Netherlands

Drugs / interventions tested

• 18F-Fluorestradiol PET/CT scan

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Amsterdam UMC, location VUmc — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Accurate staging is of great importance in patients with clinically locally advanced primary breast cancer (LABC, stage III) or locoregional recurrent (LRR) breast cancer for making a correct treatment plan. According to current guidelines, staging is performed with positron emission tomography (PET) using the 2-\[18F\]fluoro-2-deoxy-D-glucose (\[18F\]FDG) PET tracer, combined with diagnostic computed tomography (CT). However, previous studies have shown that this technique (with the current PET tracer) might not be sufficient for accurate staging. Specifically in low grade, estrogen receptor positive (ER+) breast cancer metastases can be missed due to the low metabolic activity, leading to low uptake of \[18F\]FDG. Therefore, there is a clinical need to improve staging procedures. 16α-\[18F\]-fluoro-17β-estradiol (\[18F\]FES), an ER-targeted PET tracer, allows imaging of ER+ tumor lesions regardless of their metabolic activity. Patients with clinically LABC and LRR have a 25-50% risk of distant metastases. Correct identification of distant metastases allows adaptation of the treatment plan to avoid burdensome treatment with surgery, systemic and radiotherapy in order to maintain quality of life. In case of oligometastases, correct identification increases the likelihood for cure with local treatment. In the current study we will compare disease staging with \[18F\]FES- and \[18F\]FDG PET in patients with clinically LABC/LRR breast cancer. Objective: To determine whether \[18F\]FES PET/CT improves staging for women with clinically LABC or LRR, ER+/HER2- breast cancer as compared to standard \[18F\]FDG PET/CT. Study design: Multicenter prospective study with invasive measurements. Study population: 20 LABC and 20 LRR ER+/HER2- breast cancer patients. Main study parameters/endpoints: To determine the percentage of patients with a correctly changed treatment plan according to information obtained from \[18F\]FES PET/CT compared to \[18F\]FDG PET/CT at staging and at 6 months of follow-up; to determine the percentage of metastatic lesions detected and missed with \[18F\]FES PET/CT compared to \[18F\]FDG PET/CT (at staging and during follow-up). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients will receive an intravenous cannula for tracer injection and blood sampling, causing potentially transient discomfort at the site of the cannula insertion. Tumor biopsy will be performed from an easy accessible lesion and the most frequent complications that can occur are discomfort, bleeding and (local) infection. The risk of complications from a tumor biopsy is considered low: 0.24-1.6% and 0.11-0.48% for major complications and mortality, respectively. Radiation exposure from a \[18F\]FES PET and \[18F\]FDG PET scan usually ranges between 4-11 mSv and 7-8 mSv, respectively. Radiation exposure from a diagnostic CT scan ranges between 8-14 mSv. The total radiation burden is considered justifiable when compared to the information that can be obtained from this study, in this patient group with breast cancer. Imaging with \[18F\]FES PET may improve staging for patients with breast cancer as it may show tumor lesions that could not be identified with \[18F\]FDG PET, the current standard for staging. If this is the case, the initial treatment goal and intensity can be adjusted which can have beneficial effects for the patient.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. The quest for improving the management of breast cancer by functional imaging: The discovery and development of 16α-[¹⁸F]fluoroestradiol (FES), a PET radiotracer for the estrogen receptor, a historical review.
   Katzenellenbogen JA. · · 2021 · cited 46× · PMID 32229068 · DOI 10.1016/j.nucmedbio.2020.02.007
2. Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.
   Borlongan MC, Wang H. · · 2023 · cited 30× · PMID 37305676 · DOI 10.3389/fcell.2023.1125174
3. Application of PET Tracers in Molecular Imaging for Breast Cancer.
   Boers J, de Vries EFJ, Glaudemans AWJM, Hospers GAP, et al · · 2020 · cited 25× · PMID 32627087 · DOI 10.1007/s11912-020-00940-9
4. PET Imaging Agents (FES, FFNP, and FDHT) for Estrogen, Androgen, and Progesterone Receptors to Improve Management of Breast and Prostate Cancers by Functional Imaging.
   Katzenellenbogen JA. · · 2020 · cited 19× · PMID 32718075 · DOI 10.3390/cancers12082020
5. Visual and quantitative evaluation of [¹⁸F]FES and [¹⁸F]FDHT PET in patients with metastatic breast cancer: an interobserver variability study.
   Mammatas LH, Venema CM, Schröder CP, de Vet HCW, et al · · 2020 · cited 13× · PMID 32307594 · DOI 10.1186/s13550-020-00627-z
6. [¹⁸F]FES uptake in the pituitary gland and white matter of the brain.
   Iqbal R, Menke-van der Houven van Oordt CW, Oprea-Lager DE, Booij J. · · 2021 · cited 11× · PMID 33730173 · DOI 10.1007/s00259-021-05281-8
7. The Diagnostic Accuracy of <sup>18</sup>F-FDG PET and <sup>18</sup>F-FES PET for Staging Grade 1-2 Estrogen Receptor-Positive Breast Cancer.
   Knip JJ, Iqbal R, Bonjer EC, Mammatas LH, et al · · 2025 · cited 3× · PMID 40035673 · DOI 10.1148/radiol.241850
8. <sup>18</sup>F-Fluoroestradiol PET/CT for Staging Low-Grade Estrogen Receptor-Positive Breast Cancer.
   Fowler AM. · · 2025 · PMID 40035672 · DOI 10.1148/radiol.250135