Screening Contrast-Enhanced Mammography as an Alternative to MRI (SCEMAM)

There are women for whom a screening breast MRI is clinically recommended, but not feasible either due to patient factors (body habitus, pacemaker or other implant, claustrophobia) or access (cost, other constraints). Contrast-enhanced mammography (CEM) is a potential alternative to MRI for screening that uses updated standard mammography equipment to obtain low- and high-energy images after intravenous injection of iodinated contrast (as used in CT scanning). The investigators seek to validate screening CEM as an alternative to screening MRI.

Study Overview

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

Detailed Description

This is a prospective study designed to evaluate the role of contrast enhanced mammography (CEM) in screening for breast cancer. The overarching goal of the research program is to improve cancer detection on screening, particularly in women with dense breasts. MRI depicts more cancers than other screening methods, including ultrasound. MRI is proven to both improve cancer detection and reduce clinically detected cancers ("interval cancers") after a negative screening mammogram in women with dense breasts. PA Senate Bill 595, signed into law June 30, 2020, requires insurance carriers to provide coverage for supplemental screening with MRI or ultrasound for a variety of indications. Relative to the number of women who may benefit from screening MRI, there is a shortage of equipment/capacity. Further, nearly half of women cannot have an MRI for medical or other reasons, such as claustrophobia, implanted devices, body habitus, or cost (deductible and copay apply even with the new legislation). Contrast-enhanced mammography (CEM) appears to have similar performance to MRI but has not been widely validated, particularly for screening. In order to lay the foundation for improved screening of women with dense breasts, the investigators seek to offer screening CEM as an alternative to MRI for women who meet guidelines for screening MRI but are unable to have MRI.

• Study Type: Interventional
• Enrollment (Actual): 615
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • UPMC Magee at the Lemieux Sports Complex
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15146
      • UPMC Magee Monroeville Breast Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Asymptomatic women under age 75 who are recommended for annual screening MRI and mammography based on current criteria:

   1. Women known to be at high risk for breast cancer because of known or suspected pathogenic mutation, prior chest radiation therapy at least 8 years earlier and before age 30, or estimated lifetime risk of at least 20% based on family history/prior biopsy history (22), between age 30 and 75.
   2. Women with extremely dense breasts age 40-75 (about 7% of the screening population (1)) (12).
2. Women with lobular carcinoma in situ (1% of women biopsied each year; about 0.06% of our screening population) beginning the year after diagnosis.
3. Women with a personal history of breast cancer diagnosed by age 50 or with dense breasts (21), beginning the year after diagnosis (will be recruited under separate ongoing TOCEM protocol).
4. Women with heterogeneously dense breasts and any family history of breast cancer (about 36% of the screening population has dense breasts and about 20% have a family history of breast cancer) who do not meet current high-risk criteria, beginning at age 40 or ten years prior to the age of the youngest relative but not before age 30.

Participants are expected to have medical or other reasons that they are not able to have screening breast MRI.

Exclusion Criteria:

1. Under age 30 or over age 75.
2. Pregnant or breast feeding.
3. Breast implants.
4. Breast surgery within the prior 12 months.
5. Breast signs or symptoms (lump, nipple discharge, nipple retraction, or being followed for breast abnormality on prior imaging).
6. Currently undergoing any type of systemic chemotherapy for cancer (excludes oral endocrine therapy such as aromatase inhibitors or tamoxifen).
7. Reduced kidney function with eGFR < 45 mL/min.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• 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 meet criteria for supplemental screening MRI, but who are unable to have MRI for medical/access/cost reasons, will be invited to have screening with contrast-enhanced mammography. Women will also have standard-of-care mammography/tomosynthesis per usual clinical practice.	Device: Contrast-enhanced mammography; supplemental breast cancer screening with contrast-enhanced mammography; Drug: Iodinated Contrast Media (ICM); supplemental breast cancer screening with contrast-enhanced mammography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer Detection Rate (CDR) Per 1,000 Screenings	Cancer detection rate per 1,000 screenings with CEM compared to standard mammography/tomosynthesis (DBT) alone. Interpretation and performance outcomes from the primary reader were compared between standard-of-care DBT examinations interpreted alone and DBT examinations interpreted with the addition of CEM.	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
False Positive Recall Rates	To assess changes in false positive recall rates from CEM. DBT false-positive findings for primary observer (usual care) vs DBT and CEM false positive findings for primary observer	1.5 years
Biopsy Rate	To assess changes in the biopsy rate after the addition of CEM. DBT biopsy rate for primary observer (usual care) vs DBT and CEM biopsy rate for primary observer.	1.5 years
Positive Predictive Value of Recall (PPV1)	To assess changes in positive predictive value of recall (PPV1) after the addition of CEM. DBT PPV1for primary observer (usual care) vs DBT and CEM PPV1 for primary observer.	1.5 years

Collaborators and Investigators

• Sponsor: Wendie Berg
• Collaborators: PA Breast Cancer Coalition
• Investigators: Principal Investigator: Wendie Berg, MD, PhD, University of Pittsburgh

Publications and helpful links

General Publications

• Berg WA, Vargo A, Lu AH, Berg JM, Bandos AI, Hartman JY, Zuley ML, Ganott MA, Kelly AE, Nair BE, Chough DM, Reginella RF, Wallace LP, Harnist KS, Carlin BA, Cohen CS, Hakim CM, Sumkin JH. Screening for Breast Cancer with Contrast-enhanced Mammography as an Alternative to MRI: SCEMAM Trial Results. Radiology. 2025 Jun;315(3):e242634. doi: 10.1148/radiol.242634.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Actual): May 30, 2025
• Study Completion (Actual): May 30, 2025

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast density; breast cancer supplemental screening; contrast-enhanced mammography; screening mammography
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: STUDY20110029

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
• 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