Contrast-Enhanced Mammography for Breast Abnormalities

Overseen By Suzanne Burdin, BS

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Margarita Louise Zuley

Disqualifiers: Breast implants, Pregnancy, Breast-feeding, Cancer treatment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

1855 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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%.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are actively being treated for cancer with chemotherapy, you cannot participate in the trial.

Is contrast-enhanced mammography safe for humans?

Contrast-enhanced mammography (CESM) is generally considered safe, but it involves a higher radiation dose compared to standard mammography. Some studies have reported adverse reactions related to the contrast agents used, but these are typically mild and infrequent. ^{1 2 3 4 5}

How is contrast-enhanced mammography different from other treatments for breast abnormalities?

Contrast-enhanced mammography is unique because it uses a special contrast agent to highlight blood vessels in breast tissue, providing both functional and structural information about breast lesions. This technique can help distinguish between benign and malignant lesions by showing how much blood supply they have, which is not possible with standard mammography. ^{1 6 7 8 9}

What data supports the effectiveness of the treatment Contrast-Enhanced Mammography for Breast Abnormalities?

Research shows that contrast-enhanced spectral mammography (CESM) improves diagnostic accuracy by reducing false-positive and false-negative results, especially in women with dense breast tissue, compared to conventional mammography. ^{1 3 10 11 12}

Who Is on the Research Team?

Margarita L Zuley, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for women aged 30 or older with suspicious breast abnormalities scheduled for a biopsy. It's not suitable for pregnant or breastfeeding women, those on chemotherapy, with reduced kidney function (eGFR < 45), known allergies to iodinated contrast, or who have a breast implant in the affected breast.

Inclusion Criteria

I am a woman.

I am scheduled for a biopsy due to a suspicious finding in my breast.

I am 30 years old or older.

Exclusion Criteria

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

I am currently receiving chemotherapy for cancer.

You have a breast implant in the breast being studied.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Diagnostic Evaluation

Participants undergo contrast enhanced mammography (CEM) to assess breast abnormalities before scheduled biopsy

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness of CEM in reducing biopsy recommendations

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Contrast Enhanced Mammography
• Iodinated Contrast Media (ICM)

Trial Overview The study tests if Contrast-Enhanced Mammography (CEM) using Iodinated Contrast Media can reduce unnecessary biopsies in cases rated BI-RADS 4A/4B while maintaining high cancer detection rates. Participants will undergo CEM before their planned biopsy to evaluate its effectiveness.

How Is the Trial Designed?

Group I: contrast enhanced mammography Experimental Treatment 2 Interventions

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.

Contrast Enhanced Mammography is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Contrast-Enhanced Mammography for:

• Breast cancer screening
• Evaluation of breast abnormalities
• Preoperative staging of breast cancer
• Monitoring response to neoadjuvant chemotherapy

Approved in United States as Contrast-Enhanced Mammography for:

• Breast cancer screening
• Evaluation of breast abnormalities
• Preoperative staging of breast cancer
• Monitoring response to neoadjuvant chemotherapy

Approved in Canada as Contrast-Enhanced Mammography for:

• Breast cancer screening
• Evaluation of breast abnormalities
• Preoperative staging of breast cancer
• Monitoring response to neoadjuvant chemotherapy

Who Is Running the Clinical Trial?

Margarita Louise Zuley

Lead Sponsor

Trials

1

Recruited

1,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Contrast-enhanced spectral mammography (CESM) significantly improves diagnostic accuracy compared to conventional mammography, achieving 100% sensitivity and 87.7% specificity in a study of 113 women referred from a breast cancer screening program.

CESM not only outperforms mammography in detecting breast cancer but also shows comparable results to MRI and histopathology in assessing the extent of cancer, making it a valuable tool even in populations with lower disease prevalence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced spectral mammography in patients referred from the breast cancer screening programme. Lobbes, MB., Lalji, U., Houwers, J., et al.[2022]

Dual-energy contrast-enhanced mammography (CESM) is a promising new imaging technique for breast cancer that aims to overcome the limitations of traditional methods like MRI and CT, which can be expensive and expose patients to high radiation doses.

The review highlights both the advantages of CESM, such as improved imaging capabilities, and its drawbacks, indicating a need for further research to optimize its use in breast care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced spectral mammography (CESM). Daniaux, M., De Zordo, T., Santner, W., et al.[2018]

Contrast-enhanced spectral mammography (CESM) significantly improves the accuracy of breast cancer detection by reducing false-positive and false-negative results while maintaining high sensitivity.

The study highlights that many artifacts affecting image quality in CESM can be easily resolved, providing valuable insights for practitioners to enhance the effectiveness of this imaging technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced Spectral Mammography: Modality-Specific Artifacts and Other Factors Which May Interfere with Image Quality. Bhimani, C., Li, L., Liao, L., et al.[2018]

Contrast-enhanced spectral mammography (CESM) demonstrated significantly higher sensitivity (86.2%) and specificity (94.1%) compared to conventional digital mammography (MMG), which had a sensitivity of only 53.4% and specificity of 85.9%, based on a study of 143 breasts from 72 women.

CESM was particularly effective in detecting breast cancer in dense breasts, identifying 80% of malignancies that MMG missed, suggesting that CESM could reduce false negatives in this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts. Mori, M., Akashi-Tanaka, S., Suzuki, S., et al.[2019]

Dual-energy contrast-enhanced spectral mammography (CESM) significantly improves the diagnosis of breast cancer in dense breasts, increasing sensitivity from 71.5% to 92.7% and accuracy from 65.9% to 85.8% compared to conventional mammography.

CESM also enhances interobserver consistency among radiologists, indicating that it provides more reliable diagnostic information regardless of the reader's experience level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in dense breasts compared to mammography alone: interobserver blind-reading analysis. Cheung, YC., Lin, YC., Wan, YL., et al.[2022]

Contrast-enhanced spectral mammography (CESM) results in a significant increase in radiation dose compared to full-field digital mammography (FFDM), with an average glandular dose (AGD) increase of 1.25 mGy (+81%) and entrance skin air kerma (ESAK) increase of 3.07 mGy (+41%).

Despite the increased radiation exposure with CESM, both CESM and FFDM doses remain within the recommended safety limits for mammography, indicating that while CESM is more intense, it is still considered safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation exposure of contrast-enhanced spectral mammography compared with full-field digital mammography. Jeukens, CR., Lalji, UC., Meijer, E., et al.[2015]

A systematic review of 84 studies involving 14,012 patients found that contrast-enhanced spectral mammography (CESM) is generally safe, with a low adverse reaction rate of 0.82%, including only one severe non-fatal reaction.

The study highlighted the need for standardization in CESM protocols, as most studies used similar parameters, such as a contrast dose of 1.5 mL/kg at a flow rate of 3 mL/s and a 120-second acquisition delay, but only half of the studies were prospective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technique, protocols and adverse reactions for contrast-enhanced spectral mammography (CESM): a systematic review. Zanardo, M., Cozzi, A., Trimboli, RM., et al.[2020]

Dual-energy contrast-enhanced spectral mammography (DE-CESM) effectively enhances the diagnosis of suspicious malignant microcalcifications, showing a high diagnostic sensitivity of 90.9% and specificity of 83.78% based on a study of 59 cases with pathological diagnoses.

The method also provides accurate measurements of cancer size, with a mean difference of only 0.05 cm compared to surgical histology, indicating its reliability for evaluating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. Cheung, YC., Tsai, HP., Lo, YF., et al.[2020]

In a study of 44 women with unclear mammogram results, contrast-enhanced dual-energy spectral mammogram (CEDM) identified 20% of lesions that were not visible on standard mammograms, highlighting its effectiveness in detecting hidden issues, especially in dense breast tissue.

CEDM not only helped in confirming the presence of lesions but also provided detailed information about their extent and characteristics, making it a valuable tool for triaging and managing breast lesions alongside traditional mammography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast enhanced dual energy spectral mammogram, an emerging addendum in breast imaging. Kariyappa, KD., Gnanaprakasam, F., Anand, S., et al.[2018]

The dual-energy contrast agent-enhanced digital subtraction mammography technique was tested on 26 subjects and successfully identified 13 cases of invasive breast cancer, demonstrating its potential efficacy in cancer detection.

The technique showed varying levels of enhancement in tumors, with most invasive cancers exhibiting strong enhancement, suggesting that it could improve the visualization of breast cancers compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced digital subtraction mammography: feasibility. Lewin, JM., Isaacs, PK., Vance, V., et al.[2022]

Dual-energy contrast-enhanced mammography is a promising new imaging technique that provides insights into the vascularization of breast lesions, which is linked to their malignancy.

Based on 15 months of clinical experience, this technique offers additional information beyond traditional mammography, helping to improve the assessment of breast lesions, although it also has its limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced mammography. Travieso Aja, MM., Rodríguez Rodríguez, M., Alayón Hernández, S., et al.[2016]

In a study analyzing 152 breast lesions (44 benign and 108 malignant) using contrast-enhanced spectral mammography (CESM), malignant lesions showed significantly stronger enhancement compared to benign ones, indicating CESM's potential for effective differentiation between lesion types.

The study found that CESM could accurately classify lesions with a sensitivity of 75.9% and specificity of 88.6%, suggesting it is a reliable tool for assessing breast lesions based on their enhancement patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative analysis of enhanced malignant and benign lesions on contrast-enhanced spectral mammography. Deng, CY., Juan, YH., Cheung, YC., et al.[2019]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Contrast-enhanced spectral mammography in patients referred from the breast cancer screening programme. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced spectral mammography (CESM). [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Contrast-enhanced Spectral Mammography: Modality-Specific Artifacts and Other Factors Which May Interfere with Image Quality. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy of contrast-enhanced spectral mammography in comparison to conventional full-field digital mammography in a population of women with dense breasts. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Diagnostic performance of dual-energy contrast-enhanced subtracted mammography in dense breasts compared to mammography alone: interobserver blind-reading analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Radiation exposure of contrast-enhanced spectral mammography compared with full-field digital mammography. [2015]

7. Germany pubmed.ncbi.nlm.nih.gov

Technique, protocols and adverse reactions for contrast-enhanced spectral mammography (CESM): a systematic review. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Contrast enhanced dual energy spectral mammogram, an emerging addendum in breast imaging. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced digital subtraction mammography: feasibility. [2022]

11. Spain pubmed.ncbi.nlm.nih.gov

Dual-energy contrast-enhanced mammography. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Quantitative analysis of enhanced malignant and benign lesions on contrast-enhanced spectral mammography. [2019]