Molecular Breast Imaging and Digital Breast Tomosynthesis in Screening Patients With Dense Breast Tissue

Study Overview
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Brief Summary
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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
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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.

Official Title
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Density MATTERS [Molecular Breast Imaging (MBI) And Tomosynthesis To Eliminate the ReServoir]

Conditions
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Breast Carcinoma

Intervention / Treatment
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* Procedure: Digital Tomosynthesis Mammography
* Radiation: Scintimammography


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Observational (MRI, DBT)<br>Participants undergo DBT and MBI at year 0 and year 1 screening. | Procedure: Digital Tomosynthesis Mammography<br>* Undergo DBT<br>* Other names: Digital Tomosynthesis of the Breast;Radiation: Scintimammography<br>* Undergo MBI<br>* Other names: Sestamibi Scintimammography;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At year 0 screening | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At year 0 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening | 
| 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. | At year 0 and year 1 screening |