Breast Cancer
Conditions
Keywords
Dense breast tissue, Breast Cancer Screening, Molecular Breast Imaging, Breast Cancer, Breast
Brief summary
We aim to compare the sensitivity of mammography to the sensitivity of Molecular Breast Imaging (a new gamma-camera based breast imaging technology) in women with dense breast tissue who are at increased risk for breast cancer.
Detailed description
The sensitivity of conventional mammography (MMO) is poor in women with mammographically dense breast parenchyma. We have developed Molecular Breast Imaging (MBI) - a new technique which utilizes a Cadmium-Zinc-Telluride (CZT) gamma camera for scintimammography that has a high sensitivity (\ 90%) for the detection of breast cancers independent of breast density. The aim of this study is to demonstrate the utility of MBI as an adjunct screening modality for the detection of occult breast cancers in women with mammographically dense breast tissue. Initial recruitment will be from the pool of patients awaiting a screening mammogram in the Department of Radiology at Mayo Clinic Rochester. All patients will have a screening MMO and an MBI study. Patients with positive studies (MBI or MMO) will undergo additional diagnostic studies. At 15 months post-recruitment, all patients will be contacted by phone or mail to determine whether subsequent to their study, there has been any change in their breast status.
Interventions
DEVICEMolecular Breast Imaging
Molecular breast imaging is a new nuclear medicine technique for imaging the breast. It uses small field of view semiconductor-based gamma cameras that use Cadmium Zinc Telluride detectors. These have superior spatial and energy resolution to conventional sodium iodide detectors.
DEVICEConventional Mammography
Mammography is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast and is used as a diagnostic and a screening tool.
Technetium (99mTc) sestamibi is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope technetium-99m bound to six methoxyisobutylisonitrile (MIBI) ligands.
Sponsors
Susan G. Komen Breast Cancer Foundation
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
FEMALE
Age
25 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Past prior screening mammography (SM) interpreted as negative or benign (This screening must have been performed at Mayo Clinic Rochester, Minnesota). 2. Past prior SM interpreted as heterogeneously dense or extremely dense (This screening must have been performed at Mayo Clinic Rochester, Minnesota). 3. Women younger than 50 years who had not undergone prior mammography, as most of these women have dense breasts. 4. Subjects had to have at least one of the following risk factors: 1. Known mutation in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) 2. History of chest, mediastinal, or axillary irradiation 3. Personal history of breast cancer 4. History of prior biopsy showing atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, or atypical papilloma 5. Gail or Claus model lifetime risk greater than or equal to 20% 6. Gail model 5 year risk greater or equal to 2.5% 7. Gail model 5 year risk greater or equal to 1.6% 8. One first-degree relative with history of breast cancer 9. Two second-degree relatives with history of breast cancer
Exclusion criteria
1. They are unable to understand and sign the consent form 2. They are pregnant or lactating 3. They are physically unable to sit upright and still for 40 minutes. 4. They have self-reported signs or symptoms of breast cancer (palpable mass, bloody nipple discharge, axillary mass etc.). 5. They have had needle biopsy within 3 months, or breast surgery within 1 year prior to the study. 6. They are currently taking tamoxifen, evista (raloxifene), or an aromatase inhibitor for adjuvant therapy or chemoprevention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic Yield | 12 months after mammography and gamma imaging | Diagnostic yield is the likelihood that a test or procedure will provide the information needed to establish a diagnosis. In this case, it is the proportion of women with positive results of a screening test and positive results with the reference standard (verified cancer status). |
| Number of Participants With Cancer Diagnosis at 12 Months | 12 months after mammography and gamma imaging | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity | 12 months after mammography and gamma imaging | Sensitivity measures the proportion of actual positives which are correctly identified as such. |
| Specificity | 12 month after mammography and gamma imaging | Specificity measures the proportion of negatives which are correctly identified as such. |
| Recall Rate | 12 months after mammography and gamma imaging | Recall rate was defined as the percentage of participants recalled for follow-up studies initiated because of abnormal findings with mammography or gamma imaging. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled between September 2005 and February 2009 in Rochester, Minnesota.
Pre-assignment details
969 subjects completed imaging and met eligibility criteria, but 33 were excluded because of lack of the reference standard (unverified cancer status).
Participants by arm
| Arm | Count |
|---|---|
| Mammography and Molecular Breast Imaging Participants underwent conventional mammography and molecular breast imaging after a 740-mBQ (20-mCi) Technetium (99mTc) sestamibi injection. | 969 |
| Total | 969 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unverified cancer status | 33 |
Baseline characteristics
| Characteristic | Mammography and Molecular Breast Imaging |
|---|---|
| Age, Continuous | 55.5 years |
| Mammographic breast density Almost entirely fat | 7 participants |
| Mammographic breast density Extremely dense | 131 participants |
| Mammographic breast density Heterogeneously dense | 702 participants |
| Mammographic breast density Scattered fibroglandular densities | 129 participants |
| Menopausal status Perimenopausal | 65 participants |
| Menopausal status Postmenopause | 529 participants |
| Menopausal status Premenopausal | 324 participants |
| Menopausal status Surgical menopause | 51 participants |
| Race or ethnicity American Indian or Alaskan Native | 1 participants |
| Race or ethnicity Asian | 6 participants |
| Race or ethnicity Black or African American | 1 participants |
| Race or ethnicity Hispanic or Latina | 1 participants |
| Race or ethnicity Unknown or data missing | 100 participants |
| Race or ethnicity White | 860 participants |
| Region of Enrollment United States | 969 participants |
| Risk factors 1 first-deg relative with history of breast cancer | 82 participants |
| Risk factors 2 second-deg relatives history of breast cancer | 85 participants |
| Risk factors Gail model 5 year risk ≥ 1.6% | 238 participants |
| Risk factors Gail model 5 year risk ≥ 2.5% | 297 participants |
| Risk factors Gail or Claus model lifetime risk ≥ 20% | 165 participants |
| Risk factors Known mutation in BRCA1 or BRCA2 gene | 5 participants |
| Risk factors personal history of breast cancer | 73 participants |
| Risk factors Prior biopsy showing hyperplasia, etc. | 23 participants |
| Risk factors Prior chest, mediastinal, or auxiliary irradiation | 1 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 | — / — |
| other Total, other adverse events | 0 / 969 |
| serious Total, serious adverse events | 0 / 969 |
Outcome results
Primary
Diagnostic Yield
Diagnostic yield is the likelihood that a test or procedure will provide the information needed to establish a diagnosis. In this case, it is the proportion of women with positive results of a screening test and positive results with the reference standard (verified cancer status).
Time frame: 12 months after mammography and gamma imaging
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Diagnostic Yield | 3.2 cancers per 1000 women screened |
| Gamma Imaging | Diagnostic Yield | 9.6 cancers per 1000 women screened |
| Both Mammography and Gamma Imaging | Diagnostic Yield | 10.7 cancers per 1000 women screened |
Comparison: Significant difference p ≤ 0.05p-value: 0.016t-test, 2 sided
Comparison: significant difference p ≤ 0.05p-value: 0.07McNemar
Primary
Number of Participants With Cancer Diagnosis at 12 Months
Time frame: 12 months after mammography and gamma imaging
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mammography Only | Number of Participants With Cancer Diagnosis at 12 Months | Invasive cancer | 7 participants |
| Mammography Only | Number of Participants With Cancer Diagnosis at 12 Months | Ductal carcinoma in situ (DCIS) | 4 participants |
Secondary
Recall Rate
Recall rate was defined as the percentage of participants recalled for follow-up studies initiated because of abnormal findings with mammography or gamma imaging.
Time frame: 12 months after mammography and gamma imaging
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Recall Rate | 9 percentage of participants |
| Gamma Imaging | Recall Rate | 8 percentage of participants |
| Both Mammography and Gamma Imaging | Recall Rate | 15 percentage of participants |
Comparison: significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: significant difference p ≤ 0.05p-value: 0.218McNemar
Secondary
Sensitivity
Sensitivity measures the proportion of actual positives which are correctly identified as such.
Time frame: 12 months after mammography and gamma imaging
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mammography Only | Sensitivity | Invasive cancers | 2 number of cancers diagnosed |
| Mammography Only | Sensitivity | All cancers | 3 number of cancers diagnosed |
| Mammography Only | Sensitivity | Ductal carcinoma in situ (DCIS) | 1 number of cancers diagnosed |
| Gamma Imaging | Sensitivity | Invasive cancers | 7 number of cancers diagnosed |
| Gamma Imaging | Sensitivity | All cancers | 9 number of cancers diagnosed |
| Gamma Imaging | Sensitivity | Ductal carcinoma in situ (DCIS) | 2 number of cancers diagnosed |
| Both Mammography and Gamma Imaging | Sensitivity | All cancers | 10 number of cancers diagnosed |
| Both Mammography and Gamma Imaging | Sensitivity | Ductal carcinoma in situ (DCIS) | 3 number of cancers diagnosed |
| Both Mammography and Gamma Imaging | Sensitivity | Invasive cancers | 7 number of cancers diagnosed |
Comparison: For all cancers; significant difference p ≤ 0.05p-value: 0.016McNemar
Comparison: For all cancers; significant difference p ≤ 0.05p-value: 0.07McNemar
Comparison: For invasive cancers; significant difference p ≤ 0.05p-value: 0.063McNemar
Comparison: For invasive cancers; significant difference p ≤ 0.05p-value: 0.063McNemar
Comparison: For ductal carcinoma in situ; significant difference p ≤ 0.05p-value: 0.5McNemar
Comparison: For ductal carcinoma in situ; significant difference p ≤ 0.05p-value: >0.99McNemar
Secondary
Specificity
Specificity measures the proportion of negatives which are correctly identified as such.
Time frame: 12 month after mammography and gamma imaging
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging). The number of participants negative for breast cancer was 936-11 = 925.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Specificity | 840 number of true negatives |
| Gamma Imaging | Specificity | 861 number of true negatives |
| Both Mammography and Gamma Imaging | Specificity | 788 number of true negatives |
Comparison: significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: significant difference p ≤ 0.05p-value: 0.069McNemar