Tomosynthesis Mammographic Imaging Screening Trial

Study Overview
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Brief Summary
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A randomized screening trial to compare the diagnostic accuracy of screening for breast cancer with three-dimensional digital breast tomosynthesis (DBT) plus two-dimensional full-field digital mammography (FFDM) versus FFDM alone.

Detailed Description
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The Tomosynthesis Mammography Imaging Screening Trial (TMIST) LEAD-IN is being conducted to ensure that all Eastern Cooperative Oncology Group / American College of Radiology Imaging Network (ECOG/ACRIN) TMIST components are properly functional and to provide an opportunity for fine tuning before launching the full TMIST. The accrual target for TMIST LEAD-IN is 6354 participants (one tenth of the projected enrollment target for TMIST) at three lead-in study sites: 1. Sunnybrook Health Sciences Centre in Toronto, 2. Vancouver (under the auspices of the Screening Mammography Programme of British Columbia) and 3. The Ottawa Hospital.

Official Title
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Tomosynthesis Mammography Imaging Screening Trial Lead-in

Conditions
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Breast Cancer

Intervention / Treatment
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* Device: Tomosynthesis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asymptomatic women age 40 and over Scheduled for screening mammogram Able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol Willing and able to provide a written informed consent. Exclusion Criteria: Presenting for mammography with symptoms of breast disease Have new breast complaints (e.g. lump, nipple discharge) Have had a mammogram of both breasts within the last 11 months Previous personal history of breast cancer Has breast enhancements (e.g. implants or injections) Pregnancy or intent to become pregnant.

Ages Eligible for Study
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Minimum Age: 40 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: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tomosynthesis + FFDM<br>Women enrolled to DBT Arm will undergo manufacturer-defined DBT | Device: Tomosynthesis<br>* Three-dimensional imaging of both breasts in standard CC and MLO views<br>|
| No Intervention: FFDM - Standard of Care for Screening<br>Women enrolled to the FFDM Arm will undergo bilateral digital mammogram with standard CC and MLO views acquired | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic Accuracy of DBT vs FFDM - AUC under ROC comparison | To compare the diagnostic accuracy using the area under the curve (AUC) score generated by receiver operator characteristic (ROC) analysis of digital breast tomosynthesis plus full-field digital mammography (DBT) versus full-field digital mammography (FFDM) alone for breast cancer screening. The examinations will be interpreted by local Breast Imaging radiologists. Cancer status will be pathologically confirmed. The women would undergo three consecutive screening rounds in the assigned arm followed by one year of standard of care imaging follow-up. | 3 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recall Rates | To compare the recall rates due to abnormal screening examinations for DBT versus FFDM when used for breast cancer screening. | 3 year | 
| Interval Cancers | To compare the number of interval cancers missed with DBT versus FFDM use in breast cancer screening. | 3 year | 
| Prevalence of Breast Cancer Subtypes | To estimate the prevalence of breast cancer subtypes (Luminal A, Luminal B, HER2neu, Basal-like, Claudin-low) by DBT and FFDM, stratified on whether cancers were detected in screening or as interval cancers. | 3 year | 
| Clinical Characteristics of Cancers | To assess and compare clinical characteristics (e.g. stage, grade, ER, PR, and HER2status) of cancers detected from screening by DBT and FFDM. Approximately 75 genes will be assayed in tumors detected in each arm of the study to evaluate breast cancer molecular subtype. | 3 year | 
| Reader Studies of variations of DBT vs FFDM - AUC under ROC comparison | To assess different combinations of FFDM, tomosynthesis and synthesized FFDM images in reader studies to assist in determining the optimum balance between radiation exposure and technique. AUC of ROC curves will be used to compare combinations. A panel of radiologists will read the various combinations of images in random order to assess whether tomosynthesis with synthetic 2D images is as accurate as tomosynthesis with FFDM images. The latter will require more radiation exposure. | 4 year | 
| Biomarker Correlation | Biomarker correlation to characterize disease in the tumor and compare to the tissue immediately adjacent to it. | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tomosynthesis, Digital Breast Tomosynthesis (DBT), Breast Imaging, Full-field digital mammography, Breast screening