Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

Positron Emission Tomography/Magnetic Resonance Imaging of Estrogen Receptor Expression n Non-Invasive Breast Cancer

This prospective, one-arm study which will enroll participants with biopsy-proven DCIS scheduled for diagnostic breast MRI for preoperative staging/extent of disease evaluation as part of standard of care. Eligible participants will be consented for participation in the research study which includes a directed breast PET/MRI with 18F-FES. 18F-FES uptake of the known malignancy will be measured on the PET/MRI examination using standardized uptake values (SUV) and tumor-to-normal tissue ratios.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Ductal Carcinoma in Situ - Category
• Intervention / Treatment: Drug: (18F)FES; Drug: Gadobenate dimeglumine

Detailed Description

Integrated whole-body magnetic resonance imaging (MRI)-positron emission tomography (PET) scanners have recently been introduced for clinical use. This technology combines the anatomic and perfusion data obtained with Dynamic Contrast Enhanced (DCE) MRI with functional imaging data obtained from PET. For breast imaging, the combination of MRI and PET has important potential to improve diagnostic accuracy and provide molecular characterization of breast cancer. The overall purpose of this research is to determine the technical feasibility of simultaneous breast DCE MRI with 18F-FES PET for measuring estrogen receptor (ER) in patients with ductal carcinoma in situ (DCIS) and identifying patients with low-risk of disease recurrence. The hypothesis is that quantitative 18F-FES uptake parameters from PET/MRI will correlate well with the ER immunohistochemistry score and with low-risk recurrence scores.

Primary Objective 1) To compare quantitative 18F-FES uptake of biopsy-proven DCIS measured using PET/MRI with ER protein levels determined by immunohistochemistry.

Secondary Objectives

1. To determine the optimal cut-point 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS
2. To determine the test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake
3. To determine the optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS
4. To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100)
5. To measure the upgrade rate to invasive cancer at surgical excision
6. To correlate tumor 18F-FES uptake with serum estradiol and sex hormone binding globulin levels.

Exploratory Objective

1) To correlate tumor cell density with 18F-FES uptake on PET/MRI

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of biopsy-proven DCIS without invasion or microinvasion measuring at least 1.0 cm in diameter by any imaging modality
• Undergoing diagnostic breast MRI ordered by the referring clinician for staging and extent of disease

Exclusion Criteria:

• Inability or unwillingness to provide informed consent to the study
• Surgery, radiation, neoadjuvant chemo/endocrine therapy for the current malignancy prior to study enrollment
• Participants currently taking or have taken an ER-blocking medication (e.g. tamoxifen, raloxifene) within 6 weeks prior to study enrollment
• Pregnant or lactating women
• Participant with intolerance or contraindications for MRI or gadolinium-based contrast agents
• Participant girth exceeds the bore of the MRI/PET scanner
• Participants with a history of allergic reaction attributable to compounds of similar chemical or biologic composition to 18F-FES
• Participants in liver failure as judged by the patient's physician, due to the hepatobiliary clearance of 18F-FES

• Participants requiring intravenous (IV) conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI will be allowed to participate as long as the following criteria are met:

  • The participant has their own prescription for the medication
  • The informed consent process is conducted prior to the self-administration of this medication
  • They come to the research visit with a driver or an alternative plan for transportation (e.g. Uber, taxi, etc.)

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: Research Arm; Directed breast PET/MRI with 18F-FES; 18F-FES uptake of the known malignancy to be measured on the PET/MRI examination

Drug: (18F)FES; 18F-FES is an investigational new drug which will be used for this study. For complete information, please refer to the Investigator's Brochure: "[18F]Fluoroestradiol: An investigational positron emission tomography (PET) radiopharmaceutical for injection, intended for use as an in vivo diagnostic for imaging estrogen receptors in tumors; Other Names: FES; 11.2 16α-[18F]-fluoro-17β-estradiol; Drug: Gadobenate dimeglumine; Gadolinium-based intravenous contrast agent used for the MRI portion of this study; Other Names: MultiHance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18F-FES Uptake in DCIS	18F-FES uptake of biopsy-proven ductal carcinoma in situ (DCIS) measured using PET/MRI will be reported in Standardized Uptake Values (SUV).	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Sex Hormone Binding Globulin Levels	A correlation analysis of sex hormone binding globulin levels will be performed using Pearson's or Spearman's rank correlation. Scatter plots, correlation coefficients (rho) and 95% confidence intervals will be reported.	1 day
Prognostic Risk Categories Determined Using Van Nuys Prognostic Index, the MSKCC Nomogram	ROC curve analysis will be performed to determine the optimal cut-point for 18F-FES SUVmax to distinguish low-risk DCIS and intermediate/high-risk DCIS. Risk categories will be determined using the Van Nuys Prognostic Index, the Memorial Sloan-Kettering Cancer Center Nomogram, and the research-based Oncotype DX DCIS score. Sensitivity and specificity will be determined with two-sided 95% confidence intervals. The area under the curve (AUCs) for the ROCs and their respective two-sided 95% confidence intervals will be calculated using logistic regression. The optimal cut-off point will be determined by considering the 18F-FES uptake value with the maximum sensitivity and specificity. This analysis will be done separately for each risk assessment model.	2 months
Research-based Oncotype DX DCIS Scores	To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100), scatter plots of continuous quantitative 18F-FES uptake (SUVmax) on the y-axis and research-based Oncotype DX DCIS scores (unitless) on the x-axis will be created to explore the distribution of the measurements. Pearson's or Spearman's rank correlation will be used to evaluate the association between quantitative 18F-FES uptake and research-based Oncotype DX DCIS score. The correlation coefficient (rho) and 95% confidence interval will be reported.	12 months
Number of Participants With Invasive Cancer at Surgical Excision	This percentage will be calculated by dividing the number of patients with invasive breast cancer diagnosed at the time of surgical excision by the number of patients with percutaneous biopsy-proven DCIS in the study.	2 months
Serum Estradiol Levels	Mean serum estradiol levels will be reported to summarize the outcome measure.	1 day

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Cancer Institute (NCI); National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Amy Fowler, University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): January 2, 2024
• Study Completion (Actual): January 2, 2024

Study Registration Dates

• First Submitted: October 9, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Breast Carcinoma In Situ; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: UW18063; A539300 (Other Identifier: UW Madison); SMPH/RADIOLOGY/RADIOLOGY (Other Identifier: UW Madison); P30CA014520 (U.S. NIH Grant/Contract); 2018-0814 (Institutional Review Board); KL2TR000428 (U.S. NIH Grant/Contract); NCI-2018-02281 (Registry Identifier: NCI Trial ID); Protocol Version 5/11/2022 (Other Identifier: UW Madison)

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