Estrogen Receptor Expression in Breast Cancer - Assessed With Positron Emission Mammography (PEM-FES)

Assessment of the Heterogeneity of Estrogen Receptor Expression in Patients With Estrogen Receptor Positive Breast Cancer Using F-18 Fluoroestradiol and High Resolution Positron Emission Mammography

The primary objective of this study is to determine the correlation between the distribution of F-18 FES within ER+ breast tumors as seen on Positron Emission Mammography (PEM) images of the breast, and the distribution of cells stained ER+ within the tumor by immunohistochemistry (IHC) measurements at surgical pathology. The secondary aim is to determine if the correlation (or lack of) between F-18 FES uptake and F-18 FDG uptake as imaged by PEM, is an accurate representation of the heterogeneity of ER expression in the tumor.

Study Overview

• Status: Withdrawn
• Conditions: Breast Neoplasm
• Intervention / Treatment: Diagnostic test: F-18 FES; Diagnostic test: F-18 FDG

Detailed Description

This pilot study will recruit up to 20 patients with newly diagnosed ER+ breast cancer who have recently undergone or are scheduled to undergo a clinically-indicated breast MRI examination and are scheduled for surgical excision of the breast cancer. All patients will undergo two PEM studies, one with F-18 FDG and the second with F-18 FES. As F-18 FES is not an FDA-approved radiopharmaceutical, this FES study will be performed under an investigator IND cross-referenced to the National Cancer Institute IND 79,005 for F-18 FES. A time interval of 6-8 hours will be required between performance of the F-18 FDG study and the F-18 FES study. All patients will have the 2 PEM studies within 30 business days of the clinically indicated MRI. See Study Schema shown below. Subjects must meet the following eligibility criteria:

1. Postmenopausal women, as defined by a. Lack of menstrual periods for ≥ 12 months b. For women with prior hysterectomy and age < 60, a serum FSH level within the postmenopausal range
2. Histologic proof of invasive breast carcinoma that is ER positive per ASCO/CAP guidelines (staining in ≥ 1% of cells by immunohistochemistry)
3. Extent of disease confirmed, or to be confirmed, on a clinical contrast-enhanced breast MRI examination
4. Minimum size criteria for index cancer of 10 mm as measured on mammogram, ultrasound, or MRI.
5. Planned surgical excision of the breast cancer at Mayo Clinic, Rochester

Study participants will be consented prior to undergoing the PEM studies. The order in which the PEM and MRI studies are performed will NOT be randomized, and will be dictated by patient schedule. Co-registration of the PEM images from F-18 FDG and F-18 FES will be used to assess the heterogeneity of uptake of the F-18 FES relative to that of F-18 FDG. Heterogeneity of ER expression in the tumor will be determined by immunohistochemistry on the pathologic tissue and findings will then be correlated with the ratio of activity in the co-registered images of F-18 FES and F-18 FDG. An integrated interpretation of the MRI and PEM images will be performed to match lesions seen on the three scans and will be made available to the ordering physician and surgeon.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Eligible patients will be offered enrollment if the time interval between initial diagnosis and surgery allows for performance of the PEM studies with both F18 FDG and F-18 FES, and they meet the following criteria:

• Postmenopausal women, as defined by

  • Lack of menstrual periods for ≥ 12 months
  • For women with prior hysterectomy and age < 60, a serum FSH level within the postmenopausal range
• Histologic proof of invasive breast carcinoma that is ER positive per ASCO/CAP guidelines (staining in ≥ 1% of cells by immunohistochemistry)
• Extent of disease confirmed, or to be confirmed, on a clinical contrast-enhanced breast MRI examination
• Minimum size criteria for index cancer of 10 mm as measured on mammogram, ultrasound, or MRI.
• Planned surgical excision of the breast cancer at Mayo Clinic, Rochester

Exclusion Criteria:

Patients are excluded if they meet any of the following criteria:

• Premenopausal
• Unable to undergo PEM scanning (weight limit of 300 lbs. on PEM system or inability to lie prone for 30 minutes)
• Total serum bilirubin > 1.5 x upper limit of normal (abnormal hepatic metabolism may interfere with FES hepatic excretion),
• Serum creatinine > 1.5 x upper limit of normal
• Patients who have received, are currently receiving, or planning to receive neoadjuvant systemic therapy prior to surgical excision
• Patients who will undergo core needle biopsy of the breast or axilla between the breast MRI and investigational PEM studies. NOTE: Axillary ultrasound with or without fine needle aspiration of an axillary mass or lymph node is allowed.
• Patients with breast implants?

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: FES vs FDG; All patients will undergo two PEM studies, one with F-18 FDG and the second with F-18 FES. Co-registration of the PEM images from F-18 FDG and F-18 FES will be used to assess the heterogeneity of uptake of the F-18 FES relative to that of F-18 FDG. Heterogeneity of ER expression in the tumor will be determined by immunohistochemistry on the pathologic tissue	Diagnostic test: F-18 FES; Evaluate uptake of F-18 FES in breast tissue; Diagnostic test: F-18 FDG; Evaluate uptake of F-18 FDG in breast tissue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation of FES and estrogen receptors	The primary objective of this study is to determine the correlation between F-18 FES uptake on PEM, and distribution of ER+ tissue on pathology	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation of FES and FDG in breast tumors	The secondary aim is to determine if the correlation (or lack of) between F-18 FES uptake and F-18 FDG uptake as imaged by PEM, is an accurate representation of the heterogeneity of ER expression in the tumor.	1 year

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael K O'Connor, Ph.D, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2018
• Primary Completion (ACTUAL): April 30, 2019
• Study Completion (ACTUAL): April 30, 2019

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (ACTUAL): August 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2019
• Last Update Submitted That Met QC Criteria: May 7, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Positron Emission Mammography
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: 16-007764

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: Yes