Breast Cancer
Conditions
Keywords
breast cancer
Brief summary
The investigators have studied the potential of breast computed tomography (bCT) for breast imaging under an NIH-funded Biomedical Research Partnership (BRP) grant (R01 EB002138-10), and 4 breast CT scanners have been developed that have imaged over 600 women to date (under more than one IRB-approved protocol). The BRP grant cannot be renewed, and with this (resubmitted) R01 grant application, the investigators seek to finalize the investigators' research in breast CT - The specific aims have been significantly modified as a result of the first critique, and the investigators now focus on a narrower set of remaining issues. This version of the protocol will add breast magnetic resonance imaging (MRI) to the experimental procedures.
Detailed description
Clinical evaluation: Four hundred women who will be having breast biopsy as part of their standard care (BIRADS 4 and 5) will be recruited to undergo additional imaging prior to biopsy, including (research) pre-and post-contrast enhanced breast CT imaging of both breasts, as well as (standard, FDA approved) contrast enhanced breast MRI. The potential of non-contrast enhanced breast CT will be compared using receiver operating characteristic (ROC) methodology against mammography alone, as well as with mammography + tomosynthesis. The breast CT images (including both pre-and post-contrast images) will be compared using ROC methodology against standard-of-care contrast-enhanced MRI (which includes both non-contrast and contrast images). The results of the clinical trials proposed in this investigation should provide strong evidence in regards to the potential of breast CT for breast cancer screening in the normal risk and high risk populations.
Interventions
DEVICEcomputed tomography
Computed tomography of both breasts. For all subjects, CT scanning will be performed before and after an I.V. iodinated contrast injection (100 mL).
DEVICEMRI
Breast MRI
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
35 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age at least 35 years old * Diagnostic findings from prior mammography highly suggestive of breast malignancy (BI- RADS® category 4 or BI-RADS® category 5) * Not pregnant or breast-feeding * Ability to lie motionless for up to 5 minutes
Exclusion criteria
* Recent breast biopsy * History of moderate or severe reaction to contrast agent injection * History of Allergy to Iodine * History of multiple food and/or drug allergy * Currently taking Glucophage or Glucovance (Metformin) * History of Chronic Asthma * History of Diabetes Mellitus * Renal (kidney) disease, or solitary kidney * Recent lab tests showing elevated serum creatinine (≥ 1.5 mg/dL) * Recent lab tests showing estimated glomerular filtration rate (eGFR) ≤ 60 ml/minute * Positive urine pregnancy test or currently breast-feeding * Inability to understand the risks and benefits of the study * The standard MRI contraindications apply, including but not limited to: having a pacemaker or other implanted electronic device, metal foreign bodies within the eye, aneurysm clips, heart valve prosthesis, vascular stents, coils, intrauterine devices (IUDs), inferior vena cava (IVC) filters, gunshot wounds with retained bullet fragments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Pre- and Post- Contrast Breast Computed Tomography With Pre- and Post- Contrast Magnetic Resonance Imaging. | 5 years | The specific quantitative endpoint of the analysis is the difference in area under the receiver operating characteristic curve (AUC) between contrast-enhanced breast CT (CE-bCT) and contrast-enhanced breast MRI (CE-bMRI). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Breast CT and Breast MRI Four hundred women who will be having breast biopsy as part of their standard care (BIRADS 4 and 5) will undergo pre- and post- contrast breast computed tomography and pre- and post- contrast magnetic resonance imaging.
computed tomography: Computed tomography of both breasts. For all subjects, CT scanning will be performed before and after an I.V. iodinated contrast injection (100 mL).
MRI: Breast MRI | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Subjects did not complete both CT and MRI to be evaluated in results | 13 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Breast CT and Breast MRI |
|---|---|
| Age, Continuous | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 7 Participants |
| Race (NIH/OMB) White | 45 Participants |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 57 |
| other Total, other adverse events | 0 / 57 |
| serious Total, serious adverse events | 0 / 57 |
Outcome results
Primary
Comparison of Pre- and Post- Contrast Breast Computed Tomography With Pre- and Post- Contrast Magnetic Resonance Imaging.
The specific quantitative endpoint of the analysis is the difference in area under the receiver operating characteristic curve (AUC) between contrast-enhanced breast CT (CE-bCT) and contrast-enhanced breast MRI (CE-bMRI).
Time frame: 5 years
Population: The analysis patient population includes women characterized as BIRAD's 4 and 5 patients based upon screening mammography (or tomosynthesis), who will then undergo further imaging workup based upon a positive finding on screening mammography (or tomosynthesis) or a palpable lesion. Because these women will be having a breast needle core biopsy after imaging, the lesion histopathology will be known and we can classify patients as having either benign or malignant lesions.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Breast CT and Breast MRI | Comparison of Pre- and Post- Contrast Breast Computed Tomography With Pre- and Post- Contrast Magnetic Resonance Imaging. | -0.04 probability | Standard Error 0.02 |
Comparison: The analysis is intended to evaluate non-inferiority in observer performance between CE-bCT and CE-bMRI as assessed by the area under the ROC curve (AUC). The null hypothesis is that the observed difference in average AUC for CE-bCT and CE-bMRI will be outside of a non-inferiority margin of -0.04. See below for details of the power analyses.p-value: 0.0595% CI: [0.025, 0.975]Obuchowski Rockette