Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Diseases and Abnormalities at or Before Birth

Breast Neoplasms

Congenital Abnormalities

Micronutrients

Anti-Infective Agents

All Drugs and Chemicals

Iodine

Cadexomer iodine

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.

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

contrast enhanced mammography

standard FDA-approved low osmolarity Iodine contrast agent with 350-370 mg/ml

Iodinated Contrast Media (ICM)

Suzanne Burdin, BS

Margarita L Zuley, MD

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%.

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.

eligible participants will have contrast enhanced mammography before their scheduled biopsy

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

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.

The investigators will estimate the magnitude of the reduction in biopsies of benign soft-tissue index lesions (which approximates the increase in patient-level

The investigators will evaluate PPV of biopsy recommendations pre- and post-CEM by lesions' imaging appearance (mass, distortion, etc.).

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).

The investigators will estimate and compare the corresponding improvements in PPV3 in soft-tissue and calcification index-lesion cohorts.

National Cancer Institute (NCI)

Margarita Louise Zuley

Professor

Breast Diseases

Skin Diseases

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.

supplemental breast cancer screening with contrast-enhanced mammography

Contrast-enhanced mammography

Wendie Berg, MD, PhD

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.

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.

Screening Contrast-Enhanced Mammography as an Alternative to MRI

To show significantly improved cancer detection with CEM compared to standard mammography/tomosynthesis

To show acceptably low false positive recall rates from CEM.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
CEM to Reduce Biopsy Rates for Less Than Highly Suspicious Breast Abnormalities: a Prospective Study	NCT05206331	Breast Cancer	contrast enhanc... Iodinated Contr...	30 Years -	University of Pittsburgh
Screening Contrast-Enhanced Mammography as an Alternative to MRI	NCT04764292	Breast Cancer	Contrast-enhanc... Iodinated Contr...	30 Years - 75 Years	University of Pittsburgh

Spots Global Cancer Trial Database for iodinated contrast media (icm)