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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05206331
• Other study ID #: STUDY21070030
• Secondary ID: 1R01CA258898
• Status: Recruiting
• Phase: Phase 4
• Start date: February 1, 2022
• Est. completion date: November 2026

Study information

• Verified date: June 2024
• Source: University of Pittsburgh
• Contact: Suzanne Burdin, BS
• Phone: 412-647-7385
• Email: burdins[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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%.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1855
• Est. completion date: November 2026
• Est. primary completion date: November 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years and older

Eligibility

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 < 45.

• Subject has had a prior reaction to iodinated contrast; thus a known allergy to iodinated contrast

Related Conditions & MeSH terms

• Breast Cancer
• Congenital Abnormalities

Intervention

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

Locations

Country	Name	City	State
United States	UPMC Magee-Womens Hospital	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Margarita Louise Zuley	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	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