Breast Cancer, Contralateral Breast Cancer
Conditions
Keywords
ductal breast carcinoma in situ, invasive ductal breast carcinoma, invasive lobular breast carcinoma, breast cancer in situ, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, Magnetic resonance imaging, MRI
Brief summary
RATIONALE: Diagnostic procedures such as magnetic resonance imaging (MRI) may improve the ability to detect cancer in the unaffected breast of women recently diagnosed with unilateral breast cancer. PURPOSE: Diagnostic trial to determine the effectiveness of MRI in evaluating the unaffected breast of women recently diagnosed with unilateral breast cancer.
Detailed description
OBJECTIVES: * Determine the diagnostic yield of magnetic resonance imaging (MRI) in evaluating the contralateral breast of women with a recent unilateral diagnosis of breast cancer and a negative contralateral mammogram and clinical breast exam. * Determine the sensitivity, specificity, positive predictive value for both call backs for additional imaging and biopsy recommendations, and receiver operating characteristic curves of MRI in evaluating these patients. * Determine the effect of the following patient-related factors: age (50 years old and over vs less than 50 years old), breast parenchymal density (fatty vs non fatty breast), and tumor histology (invasive lobular vs invasive ductal, invasive vs in situ) on the performance of MRI (cancer yield, sensitivity, specificity, and PPV). OUTLINE: This is a multicenter study. Patients receive gadopentetate dimeglumine IV and then undergo magnetic resonance imaging of the contralateral breast. Patients are followed at 12-18 and 24-30 months. PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.
Interventions
PROCEDUREMRI
Breast contralateral to the breast diagnosed with cancer was scanned prior to initiation of chemotherapy and within 90 days of a negative mammogram of the study breast. A recent (within 90 days) negative or benign mammogram (defined by final BI RADS category 1 or 2) and negative or benign clinical breast exam of the study breast were required for entry into the study.
Sponsors
National Cancer Institute (NCI)
American College of Radiology Imaging Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Recently confirmed unilateral ductal carcinoma in situ or invasive cancer of the breast * Confirmed by biopsy or fine needle aspiration (FNA) within the past 60 days * Negative or benign mammogram (BI-RADS assessment 1 or 2) and negative or benign clinical breast exam of the contralateral breast within the past 90 days * Prior biopsy of the contralateral breast (including FNA) is allowed provided it was performed at least 6 months prior to study entry * Prior magnetic resonance exam of the contralateral breast is allowed provided it was performed at least 1 year prior to study entry * No remote history of breast cancer * No new breast symptoms within the past 60 days for which further evaluation is recommended * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Female Menopausal status * Not specified Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Cardiovascular * No pacemaker * No magnetic aneurysm clips Other * Not pregnant * No implanted magnetic device * No severe claustrophobia * No other contraindications to MRI * No psychiatric, psychological, or other condition that would preclude informed consent PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * At least 6 months since prior anticancer chemotherapy Endocrine therapy * No concurrent therapeutic hormonal therapy, tamoxifen, or aromatase inhibitors (preventive therapy allowed) Radiotherapy * Not specified Surgery * Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI Diagnostic Yield of Cancers in the Contralateral Breast | within 90 days of a negative mammogram of the study breast | To assess the diagnostic yield of magnetic resonance imaging (MRI) in evaluating the contralateral breast of women with a recent unilateral diagnosis of breast cancer and a negative contralateral mammogram and clinical breast exam. the Test status was defined based on combinations of the following 4 factors: 1. The initial BI-RADs: from the MRI of the contralateral breast 2. The final BI-RADs: determined after all subsequent work-up and follow-up within 365 from the initial MRI (an explicit recommendation for biopsy always resulted in a final BI-RADs of 4). 3. Subsequent work-up includes all procedures resultant from an Initial MRI finding (generally triggered by a BI-RADs 0 or 3) within 365 from the initial MRI 4. Whether or not biopsy procedure (Bx) were performed on the contralateral (Study) breast within 365 from the initial MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy | within 90 days of a negative mammogram of the study breast | Accuracy values (Sensitivity, Specificity, Positive Predicative Value (PPV), Negative Predictive Value (NPV), Diagnostic Yield, and Area Under the Curve (AUC)) of MRI in evaluating the contralateral breast of women with recent personal diagnosis of breast cancer will be determine from the reference standard (a diagnosed cancer in the study breast) and the Test result defined as either the Probability of malignancy from the initial MRI interpretation (for AUC) or the Final BI-RADs, where the final BI-RADS is defined as the BI-RADS assigned after all subsequent work-up and follow-up within 365 from the initial MRI are complete (an explicit recommendation for biopsy always results in a final BI-RADs of 4). |
| AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | within 90 days of a negative mammogram of the study breast | Area Under the Curve (AUC) of MRI in evaluating the contralateral breast of women with recent personal diagnosis of breast cancer will be determine from the reference standard (a diagnosed cancer in the study breast) and the Test result defined as the Probability of malignancy from the initial MRI interpretation. |
Countries
Canada, Germany, United States
Participant flow
Recruitment details
The data includes information on 1007 participants enrolled between April 1, 2003 and June 10, 2004 at 25 centers for data collected through August 8, 2006.
Pre-assignment details
Patients were not imaged by MRI if they did not meet eligibility criteria, withdrew, or were otherwise unable to be scanned (claustrophobic, too large for scanner, illness, etc.)
Participants by arm
| Arm | Count |
|---|---|
| MRI Evaluation of Contralateral Breast The cohort is a distinct population of women at high risk for breast carcinoma: women with a recent (within 60 days) personal diagnosis of breast cancer who will have MRI to evaluate the contralateral breast.
MRI: Breast contralateral to the breast diagnosed with cancer was scanned prior to initiation of chemotherapy and within 90 days of a negative mammogram of the study breast. A recent (within 90 days) negative or benign mammogram (defined by final BI RADS category 1 or 2) and negative or benign clinical breast exam of the study breast were required for entry into the study. | 969 |
| Total | 969 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Claustrophobic | 5 |
| Overall Study | Ineligible | 20 |
| Overall Study | Poor positioning, illness,pain | 3 |
| Overall Study | technical issues | 6 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | MRI Evaluation of Contralateral Breast |
|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 925 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 2 Participants |
| Race/Ethnicity, Customized Asian | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 48 Participants |
| Race/Ethnicity, Customized Native Hawaiian Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Unknown | 14 Participants |
| Race/Ethnicity, Customized White | 887 Participants |
| Sex: Female, Male Female | 969 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,007 |
| other Total, other adverse events | 0 / 1,007 |
| serious Total, serious adverse events | 0 / 1,007 |
Outcome results
Primary
MRI Diagnostic Yield of Cancers in the Contralateral Breast
To assess the diagnostic yield of magnetic resonance imaging (MRI) in evaluating the contralateral breast of women with a recent unilateral diagnosis of breast cancer and a negative contralateral mammogram and clinical breast exam. the Test status was defined based on combinations of the following 4 factors: 1. The initial BI-RADs: from the MRI of the contralateral breast 2. The final BI-RADs: determined after all subsequent work-up and follow-up within 365 from the initial MRI (an explicit recommendation for biopsy always resulted in a final BI-RADs of 4). 3. Subsequent work-up includes all procedures resultant from an Initial MRI finding (generally triggered by a BI-RADs 0 or 3) within 365 from the initial MRI 4. Whether or not biopsy procedure (Bx) were performed on the contralateral (Study) breast within 365 from the initial MRI
Time frame: within 90 days of a negative mammogram of the study breast
Population: All eligible participants with an analyzable MRI
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up/comp bx) | Test Negative (T-) | 3 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5/work-up). | Test Positive (T+) | 31 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 4, 5) | Test Negative (T-) | 3 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5/work-up). | Test Negative (T-) | 2 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up/comp bx) | Test Positive (T+) | 30 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Final BI-RAD 0, 4, 5) | Test Positive (T+) | 30 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5) | Test Positive (T+) | 31 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Final BI-RAD 0, 4, 5) | Test Negative (T-) | 3 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 4, 5) | Test Positive (T+) | 30 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up) | Test Positive (T+) | 30 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5) | Test Negative (T-) | 2 Participants |
| Reference Standard Positive (RS+) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up) | Test Negative (T-) | 3 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5) | Test Negative (T-) | 689 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up/comp bx) | Test Positive (T+) | 91 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up/comp bx) | Test Negative (T-) | 845 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 4, 5) | Test Positive (T+) | 143 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 4, 5) | Test Negative (T-) | 793 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5) | Test Positive (T+) | 247 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up) | Test Negative (T-) | 831 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5/work-up). | Test Positive (T+) | 145 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 0, 3, 4, 5/work-up). | Test Negative (T-) | 791 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Final BI-RAD 0, 4, 5) | Test Positive (T+) | 114 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Final BI-RAD 0, 4, 5) | Test Negative (T-) | 822 Participants |
| Reference Standard Negative (RS-) | MRI Diagnostic Yield of Cancers in the Contralateral Breast | Test + (Initial MRI BI-RAD 4, 5/work-up) | Test Positive (T+) | 105 Participants |
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 0, 4 or 5 based on Final BI-RADS95% CI: [0.02, 0.042]
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 4 or 5 based on initial MRI and subsequent work-up95% CI: [0.021, 0.044]
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 4 or 5 based on initial MRI and subsequent work-up and a completed biopsy procedure95% CI: [0.02, 0.042]
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 0, 4 or 5 on the initial MRI scan95% CI: [0.02, 0.042]
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 0, 3, 4 or 5 on the initial MRI scan95% CI: [0.021, 0.043]
Comparison: Diagnostic Yield is defined as the likelihood that a test or procedure will provide the information needed to establish a diagnosis. For this analysis, a Positive Test is defined as a score of BI-RADS 0, 3, 4 or 5 based on initial MRI and subsequent work-up95% CI: [0.021, 0.043]
Secondary
AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast
Area Under the Curve (AUC) of MRI in evaluating the contralateral breast of women with recent personal diagnosis of breast cancer will be determine from the reference standard (a diagnosed cancer in the study breast) and the Test result defined as the Probability of malignancy from the initial MRI interpretation.
Time frame: within 90 days of a negative mammogram of the study breast
Population: All eligible participants with an analyzable MRI
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reference Standard Positive (RS+) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 2: Probably not malignant | 2 Participants |
| Reference Standard Positive (RS+) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 4: Probably malignant | 15 Participants |
| Reference Standard Positive (RS+) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 3: Possibly malignant | 10 Participants |
| Reference Standard Positive (RS+) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 5: Definitely malignant | 4 Participants |
| Reference Standard Positive (RS+) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 1: Definitely not malignant | 2 Participants |
| Reference Standard Negative (RS-) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 5: Definitely malignant | 2 Participants |
| Reference Standard Negative (RS-) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 1: Definitely not malignant | 565 Participants |
| Reference Standard Negative (RS-) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 2: Probably not malignant | 256 Participants |
| Reference Standard Negative (RS-) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 3: Possibly malignant | 92 Participants |
| Reference Standard Negative (RS-) | AUC as a Measure of the Accuracy of MRI for the Detection of Cancer in the Contralateral Breast | 4: Probably malignant | 21 Participants |
Comparison: ROC analysis - estimates the accuracy of MRI within 90 days of a negative mammogram to detect cancer in the contralateral breast95% CI: [0.8956, 0.9753]
Secondary
MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy
Accuracy values (Sensitivity, Specificity, Positive Predicative Value (PPV), Negative Predictive Value (NPV), Diagnostic Yield, and Area Under the Curve (AUC)) of MRI in evaluating the contralateral breast of women with recent personal diagnosis of breast cancer will be determine from the reference standard (a diagnosed cancer in the study breast) and the Test result defined as either the Probability of malignancy from the initial MRI interpretation (for AUC) or the Final BI-RADs, where the final BI-RADS is defined as the BI-RADS assigned after all subsequent work-up and follow-up within 365 from the initial MRI are complete (an explicit recommendation for biopsy always results in a final BI-RADs of 4).
Time frame: within 90 days of a negative mammogram of the study breast
Population: All eligible participants with an analyzable MRI
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reference Standard Positive (RS+) | MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy | Test + (Final BI-RAD 0, 4, 5) | 30 Participants |
| Reference Standard Positive (RS+) | MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy | Test - (Final BI-RAD 1,2,3) | 3 Participants |
| Reference Standard Negative (RS-) | MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy | Test + (Final BI-RAD 0, 4, 5) | 114 Participants |
| Reference Standard Negative (RS-) | MRI Detection of Cancer in the Contralateral Breast for the Estimation of Diagnostic Accuracy | Test - (Final BI-RAD 1,2,3) | 822 Participants |
Comparison: Sensitivity estimate - estimates the P(T+\|D+) where the MRI within 90 days of a negative mammogram is the test (T) and cancer in the contralateral breast is the Disease status(D)95% CI: [0.7567, 0.9809]
Comparison: Specificity - estimates the P(T-\|D-) of MRI where the MRI within 90 days of a negative mammogram is the test (T) and cancer in the contralateral breast is the Disease status(D)95% CI: [0.8555, 0.8985]
Comparison: PPV estimate - estimates the P(D+\|T+), where the MRI within 90 days of a negative mammogram is the test (T) and cancer in the contralateral breast is the Disease status(D).95% CI: [0.1452, 0.2839]
Comparison: B. NPV Analysis for ALL Cases in Analysis Set NPV estimate - estimates the P(D-\|T-), where the MRI within 90 days of a negative mammogram is the test (T) and cancer in the contralateral breast is the Disease status(D)95% CI: [0.9894, 0.9993]
Comparison: B. Diagnostic Yield for ALL Cases in Analysis Set Diagnostic Yield - estimates the likelihood that the MRI within 90 days of a negative mammogram will provide the information needed to establish a diagnosis95% CI: [0.021, 0.044]