Breast Cancer
Conditions
Keywords
Dense breast tissue, Breast Cancer Screening, Molecular Breast Imaging, Breast Cancer, Breast
Brief summary
A new test for breast cancer screening, molecular breast imaging (MBI) may be more sensitive than mammography for detecting breast cancer in women with dense breasts. The purpose of this study is to see if MBI using a low dose of gamma radiation can find cancers not seen on mammography. Hypotheses: 1. Low-Dose MBI has a significantly higher sensitivity and specificity and equal or higher positive predictive value than SM in women age 40 and older with mammographically dense breasts. 2. Low-dose MBI has comparable sensitivity and specificity to that previously achieved with MBI using a higher dose of radiation. 3. MBI produces a low false positive rate (specificity \>90%) that permits its use as a screening tool in this patient population.
Detailed description
A previous study demonstrated that the addition of MBI using 20 mCi Tc-99m sestamibi to screening mammography (SM) increased diagnostic yield for breast cancer in dense breasts (supplemental yield of 7.5/1000 screened). After implementing radiation dose reduction techniques, the performance of incident SM and prevalent screen MBI in women with dense breasts will be compared. Methods: Women presenting for SM with heterogeneously or extremely dense breasts on past prior SM were enrolled and underwent digital SM and MBI. Study information was sent to all eligible patients in advance of their scheduled SM explaining the study and offering them participation. Eligible patients who requested to participate were offered an MBI on the same day as their SM or within 21 days of the SM. Participants may have participated in this screening study up to two times provided at least 24 months had elapsed since the initial MBI scan. This time period was selected as the average time for a tumor to double in size is approximately 20 months. Hence a 24 month time interval between MBI studies was to enable detection of interval cancers or cancers that were too small to be detected in the initial MBI scan. MBI was performed with 8 mCi Tc-99m sestamibi and dual-head cadmium zinc telluride detectors. SMs were read independently; MBIs were read in comparison with SM. MBIs were assigned an assessment score of 1-5 which parallels BI-RADS; scores of 3-5 on MBI were considered positive.
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
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Past prior SM interpreted as negative or benign \[Breast Imaging Reporting and Data System (BI-RADS) Category 1 or 2\] * Past prior SM interpreted as heterogeneously dense or extremely dense
Exclusion criteria
* Subject is unable to understand and sign the consent form * Subject is pregnant or lactating * Subject is physically unable to sit upright and still for 40 minutes * Subject has self-reported signs or symptoms of breast cancer (palpable mass, bloody nipple discharge, axillary mass, etc.) * Subject has had needle biopsy within 3 months, or breast surgery within 1 year prior to the study * Subject is currently taking tamoxifen, Evista (raloxifene), Zoladex or an aromatase inhibitor for adjuvant therapy or chemoprevention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Within 21 days of mammography | The cancer detection rate per 1000 women screened is the estimate of the number of women with positive results from a screening test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Specificity | Within 21 days of mammography | Specificity measures the percentage of negatives which are correctly identified as such. |
| Sensitivity for All Cancers Diagnosed | Within 21 days of mammography | Sensitivity measures the percentage of actual positives which are correctly identified as such. |
| Recall Rate | 12 months after mammography and MBI | Recall rate was defined as the percentage of participants recalled for follow-up studies initiated because of abnormal findings with mammography or MBI. |
| Biopsy Rate | 12 months after mammography and MBI | Biopsy rate = number of participants who had a biopsy/number of number of participants analyzed. |
Countries
United States
Participant flow
Recruitment details
Women for the Part B low dose study were enrolled between 5/11/2009 and 3/8/2012.
Participants by arm
| Arm | Count |
|---|---|
| Mammography and Molecular Breast Imaging Participants underwent conventional mammography and molecular breast imaging after a 740-millibecquerel (mBQ) (8-mCi) Technetium (99mTc) sestamibi injection.
Molecular 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.
Conventional 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: 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. | 1,638 |
| Total | 1,638 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unverified cancer status | 53 |
Baseline characteristics
| Characteristic | Mammography and Molecular Breast Imaging |
|---|---|
| Age, Continuous | 58.1 years |
| Breast Density of Participants with No Prior Mammogram Heterogeneously dense breasts | 5 participants |
| Breast Density of Participants with No Prior Mammogram Participants with Prior Mammogram | 1631 participants |
| Breast Density of Participants with No Prior Mammogram Scattered fibroglandular densities | 2 participants |
| Mammogram Prior to Study Entry 425-730 days | 301 participants |
| Mammogram Prior to Study Entry < 425 days | 1310 participants |
| Mammogram Prior to Study Entry >730 days | 20 participants |
| Mammogram Prior to Study Entry None | 7 participants |
| Mammographic Breast Density Almost entirely fat | 0 participants |
| Mammographic Breast Density Extremely dense | 230 participants |
| Mammographic Breast Density Heterogeneously dense | 1259 participants |
| Mammographic Breast Density Scattered fibroglandular densities | 149 participants |
| Menopausal Status Peri-menopausal | 186 participants |
| Menopausal Status Postmenopausal | 1021 participants |
| Menopausal Status Premenopausal | 355 participants |
| Menopausal Status Surgical Menopause | 76 participants |
| Molecular Breast Imaging Prior to Study Entry 415- 730 days | 8 participants |
| Molecular Breast Imaging Prior to Study Entry < 425 days | 0 participants |
| Molecular Breast Imaging Prior to Study Entry > 730 days | 171 participants |
| Molecular Breast Imaging Prior to Study Entry None | 1459 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 14 Participants |
| Race (NIH/OMB) Black or African American | 6 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 | 10 Participants |
| Race (NIH/OMB) White | 1605 Participants |
| Region of Enrollment United States | 1638 participants |
| Risk Factors 1 first-deg relative with history of breast cancer | 53 participants |
| Risk Factors 2 2nd-deg relatives with history of breast cancer | 56 participants |
| Risk Factors Chest, mediastinal, or axillary irradiation | 5 participants |
| Risk Factors Gail model 5 year risk ≥ 1.7% | 360 participants |
| Risk Factors Gail model 5 year risk ≥ 2.5% | 203 participants |
| Risk Factors Gail or Claus model lifetime risk ≥ 20% | 78 participants |
| Risk Factors Known mutation in BRCA1 or BRCA2 genes | 3 participants |
| Risk Factors None of the above risk factors | 693 participants |
| Risk Factors Personal history of breast cancer | 166 participants |
| Risk Factors Prior biopsy showing hyperplasia, etc. | 21 participants |
| Sex: Female, Male Female | 1638 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 / 1,585 |
| serious Total, serious adverse events | 0 / 1,585 |
Outcome results
Primary
Cancer Detection Rate Per 1000 Women Screened, by Breast Density
The cancer detection rate per 1000 women screened is the estimate of the number of women with positive results from a screening test.
Time frame: Within 21 days of mammography
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mammography Only | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | All densities | 3.2 cancers per 1000 women screened |
| Mammography Only | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Scattered fibroglandular densities | 0 cancers per 1000 women screened |
| Mammography Only | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Heterogeneously dense | 3.3 cancers per 1000 women screened |
| Mammography Only | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Extremely dense | 4.5 cancers per 1000 women screened |
| Mammography With Adjunct MBI | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Extremely dense | 13.6 cancers per 1000 women screened |
| Mammography With Adjunct MBI | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | All densities | 12.0 cancers per 1000 women screened |
| Mammography With Adjunct MBI | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Heterogeneously dense | 10.6 cancers per 1000 women screened |
| Mammography With Adjunct MBI | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Scattered fibroglandular densities | 21.0 cancers per 1000 women screened |
| Molecular Breast Imaging Alone | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Extremely dense | 13.6 cancers per 1000 women screened |
| Molecular Breast Imaging Alone | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Scattered fibroglandular densities | 21.0 cancers per 1000 women screened |
| Molecular Breast Imaging Alone | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | Heterogeneously dense | 9.0 cancers per 1000 women screened |
| Molecular Breast Imaging Alone | Cancer Detection Rate Per 1000 Women Screened, by Breast Density | All densities | 10.7 cancers per 1000 women screened |
Comparison: Comparison of the two groups for all densities, significant difference p ≤ 0.05.p-value: <0.001t-test, 2 sided
Comparison: Comparison of two groups for all densities; significant difference p ≤ 0.05.p-value: 0.004t-test, 2 sided
Secondary
Biopsy Rate
Biopsy rate = number of participants who had a biopsy/number of number of participants analyzed.
Time frame: 12 months after mammography and MBI
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Biopsy Rate | 1.3 percentage of participants |
| Mammography With Adjunct MBI | Biopsy Rate | 4.2 percentage of participants |
| Molecular Breast Imaging Alone | Biopsy Rate | 3.2 percentage of participants |
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
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 MBI.
Time frame: 12 months after mammography and MBI
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and MBI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Recall Rate | 11.0 percentage of participants |
| Mammography With Adjunct MBI | Recall Rate | 17.6 percentage of participants |
| Molecular Breast Imaging Alone | Recall Rate | 7.5 percentage of participants |
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
Secondary
Sensitivity for All Cancers Diagnosed
Sensitivity measures the percentage of actual positives which are correctly identified as such.
Time frame: Within 21 days of mammography
Population: The analysis population only included participants with a verified cancer status at 12 months after the initial screening. 21 participants out of the total study population of 1585 were diagnosed with cancer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Sensitivity for All Cancers Diagnosed | 23.8 percentage of actual positives |
| Mammography With Adjunct MBI | Sensitivity for All Cancers Diagnosed | 90.5 percentage of actual positives |
| Molecular Breast Imaging Alone | Sensitivity for All Cancers Diagnosed | 81.0 percentage of actual positives |
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: Significant difference p ≤ 0.05p-value: 0.004McNemar
Secondary
Specificity
Specificity measures the percentage of negatives which are correctly identified as such.
Time frame: Within 21 days of mammography
Population: The analysis population only included participants with a verified negative cancer status at 12 months after the initial screening (mammography and MBI).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mammography Only | Specificity | 89.1 percentage of true negatives |
| Mammography With Adjunct MBI | Specificity | 83.4 percentage of true negatives |
| Molecular Breast Imaging Alone | Specificity | 93.5 percentage of true negatives |
Comparison: Significant difference p ≤ 0.05p-value: <0.001McNemar
Comparison: Significant difference p ≤ 0.05p-value: <0.0001McNemar