CEM to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study

Contrast Enhanced Mammography (CEM) to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study

One of the primary criticisms of mammography is that it leads to unneeded stress and anxiety from identification and biopsy of non-cancerous findings. Contrast-enhanced mammography (CEM) has the potential to significantly reduce biopsy rates for commonly seen benign breast lesions while preserving very high cancer detection. The investigators propose a prospective clinical study of patients with diagnostic mammograms rated as BIRADS 4A or 4B and scheduled for a biopsy, in which, prior to undergoing their scheduled biopsy, a CEM procedure is performed. The investigators will test the primary hypothesis that for soft tissue lesions (i.e. masses, asymmetries, architectural distortions) initially rated BI-RADS 4A/4B adding CEM will reduce, by at least 20%, the number of biopsy recommendations for actually benign cases and, at the same time, provide a negative predictive value (NPV) higher than 95%.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: contrast enhanced mammography; Drug: Iodinated Contrast Media (ICM)

Detailed Description

The investigators believe that an operationally simple, cost effective, contrast enhanced mammogram (CEM), performed during the patient's diagnostic evaluation, would be the best approach to improve the accuracy of radiologists' decisions for need to biopsy lesions classified with mammography, tomosynthesis (DBT) or ultrasound as 4A or 4B. CEM uses iodine contrast with dual low and high KeV mammogram images to create a contrast enhancement map of the breast that directly overlays the mammogram, thus providing anatomic and kinetic information, similar to MRI. The investigators found in a preliminary clinical trial that radiologists had higher true-positive rates and lower false-positive rates for biopsy recommendation with CEM than when using DBT and ultrasound. To validate those initial findings, the investigators propose to prospectively and sequentially perform CEM on 1855 consenting women with BIRADS 4A or 4B lesions detected on mammography, DBT or ultrasound. Prospectively radiologists will provide BIRADS ratings for every lesion using DBT alone, then with ultrasound and finally with CEM. With pathology known and based on the study design to minimize case by radiologist potential biases, the investigators plan to estimate the NPV level of CEM-based recommendations (overall and within the cases with conventionally confirmed biopsy recommendation) and demonstrate that it is sufficiently high, while leading to substantial reduction in biopsy recommendations for actually benign lesions. The investigators primary expectation is that the number of recommendations to biopsy benign lesions will decrease significantly (~20%), while maintaining high NPV (>95%) among the initial recommendations.

• Study Type: Interventional
• Enrollment (Estimated): 2100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Suzanne Burdin, BS; Phone Number: 412-647-7385; Email: burdins@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • UPMC Magee-Womens Hospital
      • Contact: Suzanne Burdin, BS; Phone Number: 412-647-7385; Email: burdins@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subject is female of any race and ethnicity
• Subject is ≥30 years old
• Subject is diagnosed with a suspicious breast abnormality and is scheduled for an imaging directed breast biopsy.

Exclusion Criteria:

• Subject is unable or unwilling to undergo informed consent
• Subject has a breast implant in the breast of interest
• Subject is pregnant
• Subject is breast-feeding
• Subject is actively being treated for cancer of any type with chemotherapy
• Subject has reduced kidney function with eGFR < 30.
• Subject has had a prior reaction to iodinated contrast; thus a known allergy to iodinated contrast

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: contrast enhanced mammography; Women who have been recently diagnosed with a suspicious abnormality for which they have scheduled a breast biopsy and meet inclusion criteria will be invited to have a contrast enhanced mammography before their scheduled biopsy procedure.	Device: contrast enhanced mammography; Dual-energy contrast images; low-energy CEM images will be obtained with a kilovoltage below 35 kVp while the high-energy images will be obtained with 45-49 kVp.The average glandular dose of the CEM procedure is approximately 2.44 mGy per view; Drug: Iodinated Contrast Media (ICM); standard FDA-approved low osmolarity Iodine contrast agent with 350-370 mg/ml

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative Predictive Value (NPV)	The investigators will estimate and compare the changes in NPV of pre- and post CEM-based recommendations (where NPV is the proportion of pathology verified benign lesions out of post-CEM-downgraded to BIRADS 3 or lower).	year 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value of biopsies performed (PPV3)	The investigators will estimate and compare the corresponding improvements in PPV3 in soft-tissue and calcification index-lesion cohorts.	year 5

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequencies	The investigators will estimate the magnitude of the reduction in biopsies of benign soft-tissue index lesions (which approximates the increase in patient-level	year 5
Positive predictive value of biopsy recommendations (PPV2)	The investigators will evaluate PPV of biopsy recommendations pre- and post-CEM by lesions' imaging appearance (mass, distortion, etc.).	year 5

Collaborators and Investigators

• Sponsor: Margarita Louise Zuley
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Margarita L Zuley, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: January 4, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 3, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: STUDY21070030; 1R01CA258898 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Images may be shared with secondary investigators, including commercial companies after removal of all identifiers. All patient identification (name, patient number, birth date) will be removed from the DICOM headers of the images.
• IPD Sharing Time Frame: after publication for indefinitely
• IPD Sharing Access Criteria: secondary investigators for image analysis. Sharing via Box

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No