[18F]FES PET/CT for the Detection of Distant Metastasis in Low-grade ER-positive Stage III Breast Cancer

A Phase 2, Open-label, Non-randomized, Single Center Study Evaluating 18F-Fluoroestradiol Positron Emission Tomography/Computed Tomography for the Detection of Distant Metastases in Low-grade, Estrogen Receptor-positive Stage III Breast Cancer

This study aims to evaluate the detection rate of distant metastases using [18F]FES PET/CT in patients with low-grade, ER-positive stage III breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Stage III Breast Cancer
• Intervention / Treatment: Diagnostic test: Fluoroestradiol (18F)

Detailed Description

Breast cancer is highly prevalent, and approximately 75% of cases are estrogen receptor (ER)-positive. Stage III breast cancer carries a significant risk of distant metastasis; therefore, NCCN and ESMO guidelines recommend systemic staging with CT, bone scan, or 18F-FDG PET/CT. However, 18F-FDG PET/CT demonstrates limited sensitivity in low-grade ER-positive tumors and invasive lobular carcinoma (ILC), and can yield false positives due to inflammatory reaction or reactive hyperplasia. Thus, more accurate imaging modalities are needed in this subgroup.

18F-fluoroestradiol (18F-FES) PET/CT visualizes ER expression and has shown high concordance with histopathology. A phase III study demonstrated 77% sensitivity and 100% specificity for metastatic disease. Emerging evidence suggests that 18F-FES PET/CT may detect distant or regional lymph node metastases more accurately than standard imaging, particularly in ILC and low-grade tumors, and can influence management decisions such as surgery and radiotherapy planning.

Accurate identification of regional nodal involvement (axillary, supraclavicular, internal mammary nodes) is essential for determining the extent of axillary surgery after neoadjuvant chemotherapy and for tailoring regional nodal irradiation. Prior studies show that metabolic imaging can alter radiotherapy fields in up to 40% of patients.

The primary objective is to determine the patient-based detection rate of qualitative 18F-FES PET/CT for distant metastases. Secondary objectives include evaluating its patient-based sensitivity and specificity for distant metastases; determining the detection rate, sensitivity, and specificity for cN3 lymph node metastases (infraclavicular, supraclavicular, and internal mammary nodes); assessing the rate of management change attributable to 18F-FES PET/CT; and comparing 18F-FES PET/CT with 18F-FDG PET/CT for detection rate, diagnostic accuracy, and management impact. Exploratory analyses will examine the correlation between qualitative and quantitative 18F-FES PET/CT findings and pathological response to neoadjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sangwon Han; Phone Number: +82-2-3010-0657; Email: hswon87@amc.seoul.kr
• Study Contact Backup: Name: Jaeeun Kim; Phone Number: +82-2-3010-4572; Email: kje0216@amc.seoul.kr

Study Locations

• South Korea
  • Seoul, South Korea
    • Recruiting
    • Asan Medical Center
    • Contact: Sangwon Han; Phone Number: +82-2-3010-0657; Email: hswon87@amc.seoul.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged ≥19 years, regardless of race/ethnicity
2. Patients newly diagnosed with invasive breast cancer within 90 days prior to screening, with documented histopathological confirmation.
3. Patients diagnosed with histologically confirmed estrogen receptor-positive, histologic grade 1 or 2 primary breast cancer
4. Patients with clinical stage IIIA-IIIC disease according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system
5. Patients who have undergone, or are scheduled to undergo chest computed tomography (CT), abdominal CT, and bone scintigraphy within 90 days prior to screening before the 18F-FES PET/CT scan
6. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤2

Exclusion Criteria:

• The subject or the subject's legally authorized representative has not signed the informed consent form
• Subjects who are currently receiving systemic therapy for breast cancer (e.g., neoadjuvant chemotherapy, hormonal therapy)
• Subjects with a history of another invasive malignancy within the past 2 years (except for non-melanoma skin cancer)
• Subjects diagnosed with distant metastases on chest CT, abdominal CT, or bone scintigraphy performed within 90 days prior to screening or before the 18F-FES PET/CT scan
• Subjects for whom neither biopsy nor ≥6 months of follow-up imaging has been performed for lesions suspicious for distant metastases
• Pregnant or breastfeeding women. The following cases are considered not at risk of pregnancy: (1) physiologically postmenopausal (no menses for ≥2 years), (2) surgically sterile (history of bilateral oophorectomy or hysterectomy), (3) women of childbearing potential with a documented negative serum or urine pregnancy test within 24 hours prior to 18F-FES administration, and who agree to use effective contraception during the trial.
• Subjects with serious and/or uncontrolled and/or unstable medical conditions (e.g., congestive heart failure, acute myocardial infarction, severe pulmonary disease, chronic kidney disease, or chronic liver disease)
• Subjects who are relatives or students of the investigator, or otherwise in a dependent relationship with the investigator
• Subjects who, in the judgment of the investigator, are unable to provide complete data for the clinical trial due to personal circumstances or other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]FES PET/CT	Diagnostic test: Fluoroestradiol (18F); Images for 90 minutes after F-18 FES injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Patient based detection rate of qualitative [18F]FES PET/CT evaluation for distant metastases	Baseline (index [18F]FES PET/CT image interpretation performed within 1 week after PET/CT acquisition, prior to initiation of definitive treatment)

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient-based sensitivity and specificity of qualitative [18F]FES PET/CT evaluation for distant metastases	From baseline [18F]FES PET/CT to confirmation of reference standard, assessed up to 6 months (histopathologic confirmation or clinical and imaging follow-up ≥6 months, through multidisciplinary consensus review)
Patient-based detection rate of qualitative [18F]FES PET/CT evaluation for cN3 lymph node metastases	Baseline (index [18F]FES PET/CT image interpretation performed within 1 week after PET/CT acquisition, prior to initiation of definitive treatment)
Patient-based sensitivity and specificity of qualitative [18F]FES PET/CT evaluation for cN3 lymph node metastases	From baseline [18F]FES PET/CT to confirmation of reference standard, assessed up to 6 months (histopathologic confirmation or clinical and imaging follow-up ≥6 months, through multidisciplinary consensus review)
Patient-based change rate in clinical management based on qualitative 18F-FES PET/CT evaluation	From baseline clinical management plan (pre-[18F]FES PET/CT) to final treatment decision after [18F]FES PET/CT, assessed within 4 weeks after PET/CT
Comparative patient-based evaluation of qualitative [18F]FES PET/CT and [18F]FDG PET/CT for detection rate of distant and cN3 lymph node metastases, and rate of change in clinical management	Baseline (paired [18F]FES PET/CT and [18F]FDG PET/CT image interpretation performed within 1 week after each PET/CT acquisition)
Comparative patient-based evaluation of qualitative [18F]FES PET/CT and [18F]FDG PET/CT for sensitivity, specificity of distant and cN3 lymph node metastases, and rate of change in clinical management	From baseline PET/CT imaging to confirmation of reference standard, assessed up to 6 months (histopathologic confirmation or clinical and imaging follow-up ≥6 months)

Other Outcome Measures

Outcome Measure	Time Frame
Correlation between qualitative/quantitative [18F]FES PET/CT evaluation and response to neoadjuvant chemotherapy	From baseline [18F]FES PET/CT to post-surgical pathologic response assessment after completion of neoadjuvant chemotherapy, assessed up to 12 months

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Hyehyun Jeong, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: December 23, 2025
• First Posted (Estimated): January 2, 2026

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: breast cancer; distant metastasis; estrogen receptor; [18F]FES PET/CT
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: FES LABC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No