Breast Carcinoma, Invasive Breast Carcinoma
Conditions
Brief summary
This clinical trial investigates contrast-enhanced mammography (CEM) in detecting breast cancer. CEM is similar to standard mammography, but it includes an injection of an iodine-based contrast, which makes tissue and blood vessels more visible in scans. Diagnostic procedures, such as CEM, may increase the chance of finding breast cancers and decrease the risk of having unnecessary biopsies.
Detailed description
PRIMARY OBJECTIVE: I. To compare the accuracy of CEM and low energy (LE) images (equivalent of full field digital mammogram \[FFDM\] as the standard of care) for the detection of additional cancer sites in the affected breast and in the contralateral breast. SECONDARY OBJECTIVES: I. To evaluate the sensitivity, specificity, positive and negative predictive value of CEM compared to LE CEM images (FFDM equivalent), digital breast tomosynthesis (DBT) and ultrasound for the detection of additional malignant lesions in the ipsilateral and contralateral breast. II. To evaluate the difference of the index cancer size estimation among CEM, LE images, DBT, and ultrasound compared to pathology measurements as the ground truth. III. To evaluate the incremental cancer detection rate provided by CEM, DBT, and ultrasound (US) compared to the outside facility (OSF) diagnosis. EXPLORATORY OBJECTIVES: I. To evaluate the rate of referral to breast magnetic resonance imaging (MRI) in the study cohort. II. To evaluate the performance of MRI for breast cancer diagnosis and compare it with other imaging modalities of CEM, LE images, DBT, and US. III. To evaluate the feasibility of CEM-guided biopsy of CEM-only detected lesions. OUTLINE: Patient receive iodinated contrast agent intravenously (IV) and undergo CEM. Patients who have not undergone DBT as part of their screening or diagnostic imaging within 3 month, undergo DBT. Patients medical records are reviewed. After completion of study treatment, patients are followed up for 12 months.
Interventions
PROCEDUREContrast-Enhanced Mammography
Undergo CEM
PROCEDUREDigital Tomosynthesis Mammography
Undergo DBT
OTHERElectronic Health Record Review
Medical records reviewed
Given IV
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female patients 18 years of age or older with known invasive or in-situ breast cancer (BC) diagnosed at an outside facility and presenting to MD Anderson for staging with imaging * Female patients 18 years of age or older referred from outside institutions with imaging findings categorized as highly suspicious (Breast Imaging Reporting and Data System \[BI-RADS\] 5 or 4C) on outside imaging or on rereview by MD Anderson's radiologists and referred for staging at MD Anderson Cancer Center (MDACC) * Willingness to participate in the study and ability to provide informed consent
Exclusion criteria
* Breast surgery within 6 months * Known allergy to iodine-containing contrast agents * History of anaphylactic reaction to any substance that required hospitalization or IV placement * Renal insufficiency; hyperthyroidism * Detection of non-breast primary or metastatic cancer in the breast
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy of CEM for Incremental Cancer Detection in the Ipsilateral and Contralateral Breasts. | One timepoint (at presentation) for lesion characterization with 24 month follow-up for outcome data collection | Rate of malignancy in lesions de-novo detected on CEM at MDACC and not detected on outside facility imaging. New non-index lesions detected on CEM that had a benign/malignant outcome on image-guided biopsy, surgery, or had a 24-month imaging follow-up with no cancer development (lesion-level evaluation) \*Index lesion was defined as follows: A) Known cancer detected at an outside facility B) Highly suspicious imaging lesion detected at an outside facility, for which a consultation was requested |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | At presentation, Day 1 | Fraction of malignant lesions detected by each component of CEM |
| Percentage of Lesions That Appeared Larger on CEM | One timepoint- at presentation | Largest measurements in imaging were compared to the largest measurements in pathology and the size difference of 5mm or more was considered significant. Fraction of patients in whom CEM detected an increase in lesion size of 5 mm or more was reported and analyzed. |
| Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | 1 timepoint at presentation | Percentage of patients with a change in the number of cancers sites (unifocal, multifocal, or bilateral) compared to outside facility imaging interpretation |
| Rate of Malignancy | One timepoint (at presentation) for lesion characterisation with 24 mo follow-up for outcome data collection | Rate of RC-only detected malignancy, LE+RC detected malignancy, LE-only detected malignancy |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of Breast MRI Utilization and the Corresponding Diagnosis in the Study Cohort. | One timepoint for CEM data (at presentation) +/- 2 month (4 month total) for MRI | Percentage of patients who underwent both CEM and MRI |
| The Fraction of CEM Biopsies That Achieve Adequate Sampling of the Target. | Two timepoints- at first CEM imaging presentation and at CEM-guided biopsy (within 2 months) | Patients who required a CEM-guided biopsy and successfully underwent it with adequate tissue sampling. Percentage of all non-index CEM lesions that required a CEM biopsy. |
Countries
United States
Participant flow
Recruitment details
Eligible and interested subjects will be consented for study participation. A research staff member who is trained in the informed consent process will explain the study, invite the patients to enroll, and obtain the informed consent of women who wish to participate. Subjects may be enrolled using the approved MD Anderson procedures for remote consenting.
Participants by arm
| Arm | Count |
|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion * Female patients with known invasive or in-situ breast cancer diagnosed at an outside facility and presenting to MD Anderson for staging with imaging.
* Female patients referred from outside institutions with imaging findings categorized as highly suspicious (BI-RADS 5 or 4C) on outside imaging or on re-review by MD Anderson's radiologists, and referred for staging at MDACC. | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | IV not sustainable | 1 |
| Overall Study | Labs outside instition parameter, eGFR | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 23 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 65 Participants |
| Region of Enrollment United States | 89 participants |
| Sex: Female, Male Female | 89 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 89 |
| other Total, other adverse events | 2 / 89 |
| serious Total, serious adverse events | 0 / 89 |
Outcome results
Primary
Accuracy of CEM for Incremental Cancer Detection in the Ipsilateral and Contralateral Breasts.
Rate of malignancy in lesions de-novo detected on CEM at MDACC and not detected on outside facility imaging. New non-index lesions detected on CEM that had a benign/malignant outcome on image-guided biopsy, surgery, or had a 24-month imaging follow-up with no cancer development (lesion-level evaluation) \*Index lesion was defined as follows: A) Known cancer detected at an outside facility B) Highly suspicious imaging lesion detected at an outside facility, for which a consultation was requested
Time frame: One timepoint (at presentation) for lesion characterization with 24 month follow-up for outcome data collection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Accuracy of CEM for Incremental Cancer Detection in the Ipsilateral and Contralateral Breasts. | 41.4 % of malignancy in new CEM lesions |
Secondary
Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging
Percentage of patients with a change in the number of cancers sites (unifocal, multifocal, or bilateral) compared to outside facility imaging interpretation
Time frame: 1 timepoint at presentation
Population: Patients who had additional malignant lesions detected as a result of CEM work-up
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with unifocal cancer as detected at outside imaging | 68 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with unifocal cancer after MDACC work-up | 50 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with unknown staging as presented at outside imaging | 3 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with unknown staging after MDACC work-up | 0 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Mutlicentric/miultifocal cancer as detected at outside imaging | 11 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Mutlicentric/miultifocal cancer after MDACC work-up | 27 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with bilateral cancer at outside imaging | 1 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Incremental Cancer Detection Rate Provided by CEM, DBT and US Compared to Outside Imaging | Patients with bilateral cancer after MDACC work-up | 6 Participants |
Secondary
Percentage of Lesions That Appeared Larger on CEM
Largest measurements in imaging were compared to the largest measurements in pathology and the size difference of 5mm or more was considered significant. Fraction of patients in whom CEM detected an increase in lesion size of 5 mm or more was reported and analyzed.
Time frame: One timepoint- at presentation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Percentage of Lesions That Appeared Larger on CEM | 28 % of malignant lesions larger on CEM |
Secondary
Rate of Malignancy
Rate of RC-only detected malignancy, LE+RC detected malignancy, LE-only detected malignancy
Time frame: One timepoint (at presentation) for lesion characterisation with 24 mo follow-up for outcome data collection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Rate of Malignancy | Rate of RC-only detected malignancy (%) | 16 percentage of malignancy |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Rate of Malignancy | Rate of LE+RC detected malignancy (%) | 82 percentage of malignancy |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Rate of Malignancy | Rate of LE-only detected malignancy (%) | 8 percentage of malignancy |
Secondary
Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth.
Fraction of malignant lesions detected by each component of CEM
Time frame: At presentation, Day 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | Total number of detected lesions (index and non-index) | 164 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | Malignant index and non-index lesions | 126 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | Benign index and non-index lesions | 32 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | High-risk lesions | 6 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | RC-only detected malignant lesions | 20 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | LE+RC detected malignant lesions | 103 lesions |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Sensitivity, Specificity, Positive and Negative Predictive Value of CEM: RC (Recombined Images) and LE (Low Energy) Images, DBT (Digital Breast Tomosynthesis), and Ultrasound Compared to Pathology as the Ground Truth. | LE-only detected malignanct lesions | 3 lesions |
Other Pre-specified
Rate of Breast MRI Utilization and the Corresponding Diagnosis in the Study Cohort.
Percentage of patients who underwent both CEM and MRI
Time frame: One timepoint for CEM data (at presentation) +/- 2 month (4 month total) for MRI
Population: Study patients who underwent both breast MRI and CEM. The fraction of the patients with MRI prompting a change in management
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Rate of Breast MRI Utilization and the Corresponding Diagnosis in the Study Cohort. | Patients with breast MRI | 33 Participants |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | Rate of Breast MRI Utilization and the Corresponding Diagnosis in the Study Cohort. | MRI changed management | 20 Participants |
Other Pre-specified
The Fraction of CEM Biopsies That Achieve Adequate Sampling of the Target.
Patients who required a CEM-guided biopsy and successfully underwent it with adequate tissue sampling. Percentage of all non-index CEM lesions that required a CEM biopsy.
Time frame: Two timepoints- at first CEM imaging presentation and at CEM-guided biopsy (within 2 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | The Fraction of CEM Biopsies That Achieve Adequate Sampling of the Target. | Fraction of non-index lesions recommended for a CEM-guided biopsy (%) | 15 percentage of successful CEM biopsies |
| Contrast Enhanced Mammography for Breast Cancer Staging in Patients Referred for Second Opinion | The Fraction of CEM Biopsies That Achieve Adequate Sampling of the Target. | Fraction of successful CEM-guided biopsies (%) | 100 percentage of successful CEM biopsies |