Diagnostic Performance of [18F]FES PET/CT for Axillary LN Metastasis in Invasive Lobular Carcinoma

A Phase 2, Open-label, Non-randomized, Single-center Study to Explore the Diagnostic Performance of [18F]FES PET/CT for the Assessment of Axillary Lymph Node Metastasis in Invasive Lobular Carcinoma of the Breast

This study aims to explore the diagnostic validity of [18F]FES PET/CT for the evaluation of axillary lymph node metastasis in patients with invasive lobular breast cancer having clinically suspected or confirmed axillary lymph node metastasis.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Lobular
• Intervention / Treatment: Drug: [18F]fluoroestradiol (FES)

Detailed Description

Invasive lobular carcinoma (ILC) is known to account for about 10-15% of all invasive breast cancer and is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC). ILC is histologically characterized by the loss of E-cadherin involved in cell adhesion, which contributes to the growth and infiltration of tumors in the characteristic non-adhesive single cell layer pattern of ILC]. Therefore, ILC often has no tumors detected by physical examinations and the sensitivity of mammography being reported to be 34%, which is much lower than IDC (81%). Therefore, the diagnosis of ILC is often delayed, the tumor size is larger and the stage is higher than that of IDC at the first visit. The diagnostic accuracy of breast ultrasound for axillary lymph node metastasis is reported as 55-92% for sensitivity and 80-97% for specificity. However, in the case of ILC, the diagnostic performance is significantly lower than this. According to the previous study on ILC, mammography had 7% of sensitivity, ultrasound had 26%, and MRI had 7% in diagnosing axillary lymph node metastasis with 38% of patients having false positive results for axillary lymph node metastasis. This is related to ILC-specific metastasis patterns in which only cells are replaced by cancer cells while maintaining the normal structure of the lymph node and the absence of desmoplastic reaction. The NCCN guideline recommends that during axillary lymph node resection, resection is performed up to level III if lymph node metastasis is confirmed or suspected in axillary level II or III. Preoperative chemotherapy should be considered for lymph node metastasis of cN3 or Bulky or matted cN2 stage. Considering the limited diagnostic accuracy of those standard imaging tests for diagnosis of axillary lymph node metastasis, [18F]FES PET/CT may help change treatment strategy, such as changing the extent of axillary lymph node resection or performing neoadjuvant chemotherapy instead of upfront surgery in patients with ILC. In addition, considering that high rate of distant metastasis and limited diagnostic accuracy of preexisting imaging modality in ILC, [18F]FES PET/CT is likely to help treatment decision making by discovering unexpected distant metastases. It is reported that the implementation of [18F]FES PET/CT contributed to the change in treatment policy in about 26% of patients compared to conventional standard imaging and [18F]FDG PET/CT. Currently in South Korea, reimbursement of [18F]FES PET/CT is limited to patients with recurrent or metastatic breast cancer whose lesions are located in the cervical spine, upper thoracic, pelvic, peritoneum, pleural, and mediastinal lymph nodes.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female subjects aged 19 years or older regardless of race/ethnicity.
• Subjects with histologically confirmed estrogen receptor-positive invasive lobular breast cancer within 90 days prior to [18F]FES PET/CT imaging
• Subjects whose primary tumor of cT1-3 according to the American Joint Committee on Cancer (AJCC) 8th tumor staging system
• Subjects with suspected or confirmed axillary lymph node metastasis clinically or in imaging test (ultrasound)
• Subjects who scheduled to undergo sentinel node biopsy or axillay lymph node dissection within 90 days of [18F]FES PET/CT imaging
• Subjects whose Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 points or less

Exclusion Criteria:

• Subject or the subject's legally acceptable representative does not provide written informed consent form
• Subjects with confirmed or suspected large, bulky, matted cN2 or cN3 axillary lymph node metastases, or distant metastases.
• Previous history of ipsilateral axillary lymph node dissection, sentinel lymph node surgery, or lymph node dissection biopsy.
• Patients who are scheduled for or have undergone chemotherapy, radiotherapy, antihormone therapy, targeted therapy, or immunotherapy between [18F]FES PET/CT and pathological diagnosis
• Subjects who are pregnant or lactating. Exclusion of the possibility of pregnancy is made by one of the following: 1) Physiologically menopausal (menstruation has stopped for more than 2 years), 2) Surgically infertility (with a history of bilateral oophorectomy or hysterectomy), 3) In the case of subjects with a possibility of pregnancy, negative serum or urine pregnancy test before administration of [18F]FES has to be negative within 24 hours, and the subjects are instructed to use contraception during her participation in this study.
• Subject has concurrent severe and/or uncontrolled and/or unstable medical condition other than cancer (e.g., congestive heart failure, acute myocardial infarction, severe lung disease, chronic kidney disease or chronic liver disease).
• Subject is a relative or student of the investigator or otherwise in a dependent relationship
• Subject has already participated in this study
• Subject not being able to provide intact data for this study due to personal circumstances or other reasons in the judgment of the investigator

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: invasive lobular breast cancer; images for 90 minutes after F-18 FES injection	Drug: [18F]fluoroestradiol (FES); F-18 FES 111~222 MBq(megabecquerel) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient based sensitivity, specificity, positive predictive and negative predictive values of a qualitative [18F]FES PET/CT assessment of axillary lymph node metastasis	diagnostic accuracy of qualitative [18F]FES PET/CT analysis	90-120 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient based sensitivity, specificity, positive predictive and negative predictive values of quantitative [ 18 F]FES PET/CT evaluation for axillary lymph node metastasis	diagnostic accuracy of quatitative [18F]FES PET/CT analysis	90-120 min
Patient based sensitivity, specificity, positive predictive and negative predictive values of [18F]FES PET/CT in FNA or CNB-negative patients	Subgroup analsis of FNA or CNB-negative patients	90-120 min
Detection rate of qualitative [18F]FES PET/CT evaluation for cN3 lymph node metastasis	Unexpected N3 node detection rate	90-120 min
Detection rate of qualitative [18F]FES PET/CT evaluation for distant metastasis	Unexpected M1 detection rate	90-120 min

Collaborators and Investigators

• Sponsor: Asan Medical Center
• Investigators: Principal Investigator: Sangwon Han, Clinical Assistant Professor

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): August 20, 2024
• Study Completion (Actual): August 20, 2024

Study Registration Dates

• First Submitted: July 18, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Breast Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Carcinoma; Carcinoma, Lobular
• Other Study ID Numbers: FES lobular

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