Hybrid Molecular Imaging of ER in Breast Cancer Patients With DCIS

Study Overview
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Brief Summary
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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.

Detailed Description
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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 To determine the optimal cut-point 18F-FES uptake value for distinguishing between ER+ and ER-negative DCIS To determine the test-retest reproducibility of quantitative assessment of tumor 18F-FES uptake To determine the optimal cut-point 18F-FES uptake value for distinguishing between low-risk DCIS and intermediate/high-risk DCIS To estimate the association of quantitative 18F-FES uptake (continuous SUVmax) with research-based Oncotype DX DCIS scores (0-100) To measure the upgrade rate to invasive cancer at surgical excision 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

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

Conditions
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Breast Cancer, Ductal Carcinoma in Situ - Category

Intervention / Treatment
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* Drug: (18F)FES
* Drug: Gadobenate dimeglumine


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: This is a prospective, one-arm, observational 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Research Arm<br>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<br>* 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<br>* Other names: FES;Drug: Gadobenate dimeglumine<br>* Gadolinium-based intravenous contrast agent used for the MRI portion of this study<br>* Other names: MultiHance;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| Upgrade Rate to 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 | A correlation analysis of serum estradiol 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 | 
| 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 |