Cystic Breast Masses by Contrast Enhanced Ultrasound (CEUS)

Qualitative and Quantitative Analysis of Cystic Breast Masses by Contrast Enhanced Ultrasound: Is Biopsy Necessary?

The overarching goal of the proposed research is to evaluate whether qualitative and quantitative parameters in real time contrast enhanced ultrasound (CEUS) can aid in assessing suspicious indeterminate cystic appearing breast masses and ultimately determine whether or not an ultrasound guided biopsy is necessary. The underlying hypothesis is that breast masses (given BIRADS 4) that lack enhancement on CEUS will have a benign histology obtained by ultrasound guided core biopsy and/or surgery. Then, in the future, these non-enhancing cystic lesions can be followed and do not need biopsy intervention.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Definity

Detailed Description

Breast cancer is the most frequently diagnosed cancer in women. To diagnose these cancers, more than 1.6 million breast biopsies are performed each year in the United States, of which more than 60% have benign pathology. A large percentage of the benign biopsies show fibrocystic changes of the breast on histology. These biopsies can be avoided with better diagnostic tools identifying fibrocystic change. The Investigators propose that contrast enhanced ultrasound (CEUS) can aid in classifying and predicting if a cystic appearing breast mass is benign or malignant, and can be a supplemental imaging tool to mammography and conventional gray-scale ultrasound (US).

In standard clinical practice, if a breast mass appears to be cystic on gray-scale US but has some suspicious features which make it difficult to tell if the mass is truly cystic or solid, the decision making for follow-up versus biopsy is difficult. This leads to unnecessary biopsies (false positives) since many of these masses are a sequel of benign fibrosis and fibrocystic changes of the breast. CEUS may help classify these masses as cystic or solid. The central premise is based on the microbubble contrast agent used in CEUS, since it stays within the blood pool and will only show enhancement if a mass has solid components and has vascular flow.

The Investigators hypothesize that indeterminate cystic breast masses will not enhance on CEUS and will correlate with benign pathology. Quantitative CEUS parameters will also help classify these lesions. If this is the case, then in the future, the non-enhancing cystic breast masses will not need to be biopsied. This will decrease patient anxiety, unnecessary interventions, and save resources.

The investigators will investigate qualitative and quantitative parameters on CEUS in evaluating indeterminate cystic breast masses given BIRADS 4 and correlate these with histopathology obtained by biopsy and/or surgery. This data will help them to develop protocols to better distinguish between benign and malignant cystic appearing breast masses.

• Study Type: Observational
• Enrollment (Actual): 135

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Department of Radiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The study will be performed as a prospective study at LAC+USC in the mammography department. Our project will enroll approximately 135 women > 18 years of age with breast masses evaluated by conventional US given BIRADS 4 and recommended for ultrasound guided biopsy.

Description

Inclusion Criteria:

• >18 years of age
• recommended for an ultrasound guided biopsy due to breast mass detection

Exclusion Criteria:

• < 18 years of age
• prior history of breast cancer
• prior history of biopsy for that specific lesion
• any condition that would be a contraindication to the microbubble contrast agent used in CEUS such as pulmonary hypertension, 3cardiac shunts, and allergy to perflutren.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Breast Mass 4a-cystic; Contrast Enhanced UltraSound (CEUS) exams will be performed on a ultrasound machine for the 4a-cystic breast masses recommended for biopsy. An intravenous line (IV) line will be inserted into the vein in the arm for the administration of the contrast agent, Definity (10 µL/kg) The patient will be asked to lie on a table for the 4DCT and unenhanced CT procedure and the images will be recorded. For the contrast enhanced ultrasound, the contrast agent will be injected into the IV line. The CEUS will be performed and the images will be recorded. The contrast agent may be administered two to three more times as needed. Scanning will then be repeated with 30 and 90 seconds delay after the IV contrast administration.	Drug: Definity; The contrast agent, Definity, 10 µL/kg, will be administered through an intravenous catheter placed in an antecubital vein. Definity is an FDA approved contrast agent for cardiac studies and will be an off-label use in this study. The agent will be injected as a single intravenous bolus followed by a 10 mL saline flush (0.9% NaCl). Images will be recorded with clip function for 90 seconds following the administration of contrast while the probe is stabilized and minimal pressure applied. During this time, qualitative evaluation of tumor enhancement will be observed, and the presence of contrast uptake within the tumor will be categorized.; Other Names: Perflutren
Breast Mass 4a- non cystic; Contrast Enhanced UltraSound (CEUS) exams will be performed on a ultrasound machine for the 4a-non cystic breast masses recommended for biopsy. An intravenous line (IV) line will be inserted into the vein in the arm for the administration of the contrast agent, Definity (10 µL/kg) The patient will be asked to lie on a table for the 4DCT and unenhanced CT procedure and the images will be recorded. For the contrast enhanced ultrasound, the contrast agent will be injected into the IV line. The CEUS will be performed and the images will be recorded. The contrast agent may be administered two to three more times as needed. Scanning will then be repeated with 30 and 90 seconds delay after the IV contrast administration..	Drug: Definity; The contrast agent, Definity, 10 µL/kg, will be administered through an intravenous catheter placed in an antecubital vein. Definity is an FDA approved contrast agent for cardiac studies and will be an off-label use in this study. The agent will be injected as a single intravenous bolus followed by a 10 mL saline flush (0.9% NaCl). Images will be recorded with clip function for 90 seconds following the administration of contrast while the probe is stabilized and minimal pressure applied. During this time, qualitative evaluation of tumor enhancement will be observed, and the presence of contrast uptake within the tumor will be categorized.; Other Names: Perflutren
Breast Mass 4b; Contrast Enhanced UltraSound (CEUS) exams will be performed on a ultrasound machine for the 4b breast masses recommended for biopsy. An intravenous line (IV) line will be inserted into the vein in the arm for the administration of the contrast agent, Definity (10 µL/kg) The patient will be asked to lie on a table for the 4DCT and unenhanced CT procedure and the images will be recorded. For the contrast enhanced ultrasound, the contrast agent will be injected into the IV line. The CEUS will be performed and the images will be recorded. The contrast agent may be administered two to three more times as needed. Scanning will then be repeated with 30 and 90 seconds delay after the IV contrast administration.	Drug: Definity; The contrast agent, Definity, 10 µL/kg, will be administered through an intravenous catheter placed in an antecubital vein. Definity is an FDA approved contrast agent for cardiac studies and will be an off-label use in this study. The agent will be injected as a single intravenous bolus followed by a 10 mL saline flush (0.9% NaCl). Images will be recorded with clip function for 90 seconds following the administration of contrast while the probe is stabilized and minimal pressure applied. During this time, qualitative evaluation of tumor enhancement will be observed, and the presence of contrast uptake within the tumor will be categorized.; Other Names: Perflutren
Breast Mass 4c; Contrast Enhanced UltraSound (CEUS) exams will be performed on a ultrasound machine for the 4c breast masses recommended for biopsy. An intravenous line (IV) line will be inserted into the vein in the arm for the administration of the contrast agent, Definity (10 µL/kg) The patient will be asked to lie on a table for the 4DCT and unenhanced CT procedure and the images will be recorded. For the contrast enhanced ultrasound, the contrast agent will be injected into the IV line. The CEUS will be performed and the images will be recorded. The contrast agent may be administered two to three more times as needed. Scanning will then be repeated with 30 and 90 seconds delay after the IV contrast administration.	Drug: Definity; The contrast agent, Definity, 10 µL/kg, will be administered through an intravenous catheter placed in an antecubital vein. Definity is an FDA approved contrast agent for cardiac studies and will be an off-label use in this study. The agent will be injected as a single intravenous bolus followed by a 10 mL saline flush (0.9% NaCl). Images will be recorded with clip function for 90 seconds following the administration of contrast while the probe is stabilized and minimal pressure applied. During this time, qualitative evaluation of tumor enhancement will be observed, and the presence of contrast uptake within the tumor will be categorized.; Other Names: Perflutren

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lesions of malignant vs. benign biopsy histology	The proportion of breast masses with presence of contrast uptake on CEUS will be calculated for lesions of malignant vs. benign biopsy histology, grouped by BIRADS categories	0-2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
classification rule with the CEUS parameters	We will build a classification rule with the CEUS parameters and then assess whether this rule can classify benign or malignant BIRADS 4a cystic lesions correctly.	11-12 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Wright Foundation
• Investigators: Principal Investigator: Sandy C Lee, MD, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2016
• Primary Completion (Actual): April 29, 2018
• Study Completion (Actual): April 29, 2018

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: August 29, 2016
• First Posted (Estimate): September 2, 2016

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: May 9, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Fibrocystic Breast Disease
• Other Study ID Numbers: HS-16-00483

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided