Back to resultsMolecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue
Primary Purpose
Breast Carcinoma
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Digital Tomosynthesis Mammography
Scintimammography
Sponsored by
About this trial
This is an interventional diagnostic trial for Breast Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Patient is a consenting female age 40-75 years
- Patient is scheduled for routine screening DBT
- Patient is asymptomatic for breast disease
- Patient had heterogeneously dense or extremely dense breasts on most recent prior mammography examination (Breast Imaging Reporting and Data System [BI-RADS] c or d) within 24 months of enrollment
- Patient is able to participate fully in all aspects of the study (completing study visits and study data collection)
- Patient understands and signs the study informed consent
- Patient anticipates being able to return one year after study enrollment to complete the second round of screening
Exclusion Criteria:
- Patient is currently pregnant or plans to become pregnant during the course of the study
- Patient is currently lactating
- Patient has had a prior MBI
- Patient has had a prior whole breast ultrasound (WBUS) for screening, with either a hand-held ultrasound probe or automated system, within 12 months prior to study enrollment
- Patient has had a prior breast MRI
- Patient has had a prior contrast-enhanced mammogram (contrast enhanced spectral mammography [CESM] or contrast-enhanced digital mammography [CEDM])
- Patient is concurrently participating in any other breast imaging research studies that involve undergoing additional breast imaging tests beyond routine screening with mammography, including but not limited to contrast-enhanced mammography, WBUS, MBI, or contrast-enhanced breast MRI
- Patient has had a breast biopsy within 3 months prior to study enrollment
- Patient has had breast surgery within 12 months prior to study enrollment
- Patient is currently undergoing treatment for breast cancer or planning surgery for a high-risk breast lesion (atypical ductal hyperplasia [ADH], atypical lobular hyperplasia [ALH], lobular carcinoma in situ [LCIS], papilloma, radial scar)
- Patient is currently taking a chemoprevention agent for breast cancer risk reduction or osteoporosis prevention (tamoxifen, raloxifene, anastrazole, letrozole, exemestane)
- Patient has a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder study adherence
Sites / Locations
- Henry Ford Hospital
- Mayo Clinic in Rochester
- Toledo Clinic Cancer Centers-Toledo
- M D Anderson Cancer Center
- Mayo Clinic Health System-Franciscan Healthcare
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Observational (MRI, DBT)
Arm Description
Participants undergo DBT and MBI at year 0 and year 1 screening.
Outcomes
Primary Outcome Measures
Rate of detection of invasive cancers
Will compare the rate of detection of invasive cancers between DBT alone versus (vs.) the combination of digital breast tomosynthesis (DBT) with supplemental molecular breast imaging (MBI) at year 0 screening. For each modality, the detection rate of invasive cancers will be estimated as the proportion of participants in the analysis set who had an invasive cancer detected by the modality and verified by pathology. Because of the paired design, the primary comparison of the invasive cancer detection rates will be made using a 2-sided McNemar's test at statistical significance level alpha= 0.05.
Secondary Outcome Measures
Rate of detection of invasive cancers
Will compare the rate of detection of invasive cancers between DBT alone vs. MBI alone at Year 0 screening. The comparison will be based on a 2-sided McNemar's test at statistical significance level alpha= 0.05.
Screening performance metrics of sensitivity
Sensitivity will be estimated for each modality as the proportion of women with breast cancer who have true positive test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI. Uncertainty in the estimate of sensitivity will be quantified through a two-sided 95% confidence interval (CI) based on the binomial distribution. If a sufficient number of radiologists interpret exams from multiple patients with breast cancer, secondary analysis may also include a 95% CI and chi-squared test adjusted for clustering of results within radiologist to allow generalization to both the population of patients and the population of radiologists.
Screening performance metrics of specificity
Specificity will be estimated as the proportion of women without breast cancer who have TN test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Screening performance metrics of recall rate
Recall rate (defined as the proportion of patients recalled from the screening test for diagnostic workup among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Screening performance metrics of biopsy rate
Biopsy rate (defined as the proportion of patients in whom biopsy is generated from a particular modality among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Screening performance metrics of positive predictive value and negative predictive value
Predictive values will be estimated for each modality based on data pooled across radiologists. Positive predictive value (PPV)1 (the proportion of patients with breast cancer among patients with abnormal screening examinations), PPV3 (the proportion of breast cancers diagnosed among biopsies performed), and negative predictive value (NPV) (the proportion of patients without breast cancer among those with normal screening examinations) will be determined. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI
Will compare tumor characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI, including size, nodal status, and molecular subtype. The analysis comparing tumor characteristics will be descriptive. Size, nodal status, and molecular subtype (including estrogen and progesterone receptor status, HER-2 status, Ki-67 and Oncotype DX score as available) will be abstracted from clinical final pathology reports from all biopsies and surgeries performed. The distribution of sizes will be summarized by ordinary numeric (e.g., means, standard deviations [SDs], range) and graphical (e.g., histograms, density smoothers) summaries. Descriptive summaries of the lesions identified with MBI but not DBT and vice versa will also be calculated to understand the differences in performance should one be identified.
Change in advanced cancer rate with incorporation of MBI screening
Will assess whether the incorporation of MBI screening reduces advanced cancer rate, the rate of advanced cancers detected at Year 1 screening will be compared to the rate at Year 0 screening. The rates of advanced cancers, together with their respective 95% confidence intervals, will be estimated for Year 0 and Year 1. Comparison in the rates between Year 0 and Year 1 will utilize the test of two proportions based on exact binomial distributions.
Rate of interval cancers with incorporation of MBI screening
We will estimate the rate of interval cancers from our study and provide a 95% confidence interval.
Relative performance of DBT and MBI within subgroups categorized by breast cancer risk
The relative performance of the screening modalities (sensitivity and specificity) will be characterized separately, within subgroups of patients defined by various levels of risk. The statistical power to discern differential performances of the screening modalities among different risk subgroups may be limited due to the restricted sample size in these subgroup analyses.
Full Information
NCT ID
NCT03220893
First Posted
July 15, 2017
Last Updated
August 31, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03220893
Brief Title
Molecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue
Official Title
Density MATTERS [Molecular Breast Imaging (MBI) And Tomosynthesis To Eliminate the ReServoir]
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 14, 2017 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study compares molecular breast imaging (MBI) and digital breast tomosynthesis (DBT) in screening patients with dense breast tissue. Breast imaging may help doctors find breast cancer sooner, when it may be easier to treat. Molecular breast imaging (MBI) uses an injection of a small amount of radioactive material that is taken up in tissues of the body that are actively changing, such as breast cancer. A specialized camera, called a gamma camera, takes pictures of the gamma rays emitted by this material. MBI may detect cancers that are not visible on mammograms. This study may help researchers determine how MBI testing compares to DBT screening.
Detailed Description
PRIMARY OBJECTIVE:
I. To compare the rate of detection of invasive cancers between digital breast tomosynthesis (DBT) alone versus (vs.) the combination of DBT with supplemental MBI at year 0 screening.
SECONDARY OBJECTIVES:
I. To compare the invasive cancer detection rates of DBT alone vs. MBI alone at year 0 screening.
II. To compare the screening performance metrics of sensitivity, specificity, recall rate, biopsy rate, positive predictive value and negative predictive value for DBT and MBI.
III. To compare tumor characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI, including size, nodal status, and molecular subtype.
IV. To assess the reduction in advanced cancer rate with incorporation of MBI screening by comparing advanced cancer rate observed at year 1 screening relative to that at year 0.
V. To assess the rate of interval cancers with incorporation of MBI screening. VI. To examine the relative performance of DBT and MBI within subgroups categorized by breast cancer risk.
OUTLINE:
Participants undergo DBT and MBI at year 0 and year 1 screening.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1732 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Observational (MRI, DBT)
Arm Type
Experimental
Arm Description
Participants undergo DBT and MBI at year 0 and year 1 screening.
Intervention Type
Procedure
Intervention Name(s)
Digital Tomosynthesis Mammography
Other Intervention Name(s)
DBT, Digital Breast Tomosynthesis, Digital Tomosynthesis of the Breast
Intervention Description
Undergo DBT
Intervention Type
Radiation
Intervention Name(s)
Scintimammography
Other Intervention Name(s)
Breast-Specific Gamma Imaging, MBI, Miraluma Scan, Miraluma Test, Molecular Breast Imaging, Nuclear Medicine Breast Imaging, sestamibi breast imaging, Sestamibi Scintimammography
Intervention Description
Undergo MBI
Primary Outcome Measure Information:
Title
Rate of detection of invasive cancers
Description
Will compare the rate of detection of invasive cancers between DBT alone versus (vs.) the combination of digital breast tomosynthesis (DBT) with supplemental molecular breast imaging (MBI) at year 0 screening. For each modality, the detection rate of invasive cancers will be estimated as the proportion of participants in the analysis set who had an invasive cancer detected by the modality and verified by pathology. Because of the paired design, the primary comparison of the invasive cancer detection rates will be made using a 2-sided McNemar's test at statistical significance level alpha= 0.05.
Time Frame
At year 0 screening
Secondary Outcome Measure Information:
Title
Rate of detection of invasive cancers
Description
Will compare the rate of detection of invasive cancers between DBT alone vs. MBI alone at Year 0 screening. The comparison will be based on a 2-sided McNemar's test at statistical significance level alpha= 0.05.
Time Frame
At year 0 screening
Title
Screening performance metrics of sensitivity
Description
Sensitivity will be estimated for each modality as the proportion of women with breast cancer who have true positive test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI. Uncertainty in the estimate of sensitivity will be quantified through a two-sided 95% confidence interval (CI) based on the binomial distribution. If a sufficient number of radiologists interpret exams from multiple patients with breast cancer, secondary analysis may also include a 95% CI and chi-squared test adjusted for clustering of results within radiologist to allow generalization to both the population of patients and the population of radiologists.
Time Frame
At year 0 and year 1 screening
Title
Screening performance metrics of specificity
Description
Specificity will be estimated as the proportion of women without breast cancer who have TN test results. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Time Frame
At year 0 and year 1 screening
Title
Screening performance metrics of recall rate
Description
Recall rate (defined as the proportion of patients recalled from the screening test for diagnostic workup among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Time Frame
At year 0 and year 1 screening
Title
Screening performance metrics of biopsy rate
Description
Biopsy rate (defined as the proportion of patients in whom biopsy is generated from a particular modality among the total number of patients screened) will be estimated employing analytical strategies similar to sensitivity and specificity. McNemar's test will be used to compare rates between two modalities. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Time Frame
At year 0 and year 1 screening
Title
Screening performance metrics of positive predictive value and negative predictive value
Description
Predictive values will be estimated for each modality based on data pooled across radiologists. Positive predictive value (PPV)1 (the proportion of patients with breast cancer among patients with abnormal screening examinations), PPV3 (the proportion of breast cancers diagnosed among biopsies performed), and negative predictive value (NPV) (the proportion of patients without breast cancer among those with normal screening examinations) will be determined. Will be analyzed to compare performance of DBT alone vs. MBI alone, and DBT alone vs. the combination of DBT with supplemental MBI.
Time Frame
At year 0 and year 1 screening
Title
Characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI
Description
Will compare tumor characteristics of all cancers (invasive and noninvasive) detected on DBT and MBI, including size, nodal status, and molecular subtype. The analysis comparing tumor characteristics will be descriptive. Size, nodal status, and molecular subtype (including estrogen and progesterone receptor status, HER-2 status, Ki-67 and Oncotype DX score as available) will be abstracted from clinical final pathology reports from all biopsies and surgeries performed. The distribution of sizes will be summarized by ordinary numeric (e.g., means, standard deviations [SDs], range) and graphical (e.g., histograms, density smoothers) summaries. Descriptive summaries of the lesions identified with MBI but not DBT and vice versa will also be calculated to understand the differences in performance should one be identified.
Time Frame
At year 1 screening
Title
Change in advanced cancer rate with incorporation of MBI screening
Description
Will assess whether the incorporation of MBI screening reduces advanced cancer rate, the rate of advanced cancers detected at Year 1 screening will be compared to the rate at Year 0 screening. The rates of advanced cancers, together with their respective 95% confidence intervals, will be estimated for Year 0 and Year 1. Comparison in the rates between Year 0 and Year 1 will utilize the test of two proportions based on exact binomial distributions.
Time Frame
At year 0 and year 1 screening
Title
Rate of interval cancers with incorporation of MBI screening
Description
We will estimate the rate of interval cancers from our study and provide a 95% confidence interval.
Time Frame
At year 0 and year 1 screening
Title
Relative performance of DBT and MBI within subgroups categorized by breast cancer risk
Description
The relative performance of the screening modalities (sensitivity and specificity) will be characterized separately, within subgroups of patients defined by various levels of risk. The statistical power to discern differential performances of the screening modalities among different risk subgroups may be limited due to the restricted sample size in these subgroup analyses.
Time Frame
At year 0 and year 1 screening
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Patient is a consenting female age 40-75 years
Patient is scheduled for routine screening DBT
Patient is asymptomatic for breast disease
Patient had heterogeneously dense or extremely dense breasts on most recent prior mammography examination (Breast Imaging Reporting and Data System [BI-RADS] c or d) within 24 months of enrollment
Patient is able to participate fully in all aspects of the study (completing study visits and study data collection)
Patient understands and signs the study informed consent
Patient anticipates being able to return one year after study enrollment to complete the second round of screening
Exclusion Criteria:
Patient is currently pregnant or plans to become pregnant during the course of the study
Patient is currently lactating
Patient has had a prior MBI
Patient has had a prior whole breast ultrasound (WBUS) for screening, with either a hand-held ultrasound probe or automated system, within 12 months prior to study enrollment
Patient has had a prior breast MRI
Patient has had a prior contrast-enhanced mammogram (contrast enhanced spectral mammography [CESM] or contrast-enhanced digital mammography [CEDM])
Patient is concurrently participating in any other breast imaging research studies that involve undergoing additional breast imaging tests beyond routine screening with mammography, including but not limited to contrast-enhanced mammography, WBUS, MBI, or contrast-enhanced breast MRI
Patient has had a breast biopsy within 3 months prior to study enrollment
Patient has had breast surgery within 12 months prior to study enrollment
Patient is currently undergoing treatment for breast cancer or planning surgery for a high-risk breast lesion (atypical ductal hyperplasia [ADH], atypical lobular hyperplasia [ALH], lobular carcinoma in situ [LCIS], papilloma, radial scar)
Patient is currently taking a chemoprevention agent for breast cancer risk reduction or osteoporosis prevention (tamoxifen, raloxifene, anastrazole, letrozole, exemestane)
Patient has a known history of any condition or factor judged by the investigator to preclude participation in the study or which might hinder study adherence
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carrie B Hruska
Organizational Affiliation
Mayo Clinic in Rochester
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Toledo Clinic Cancer Centers-Toledo
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623
Country
United States
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Mayo Clinic Health System-Franciscan Healthcare
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Molecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue
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