Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography

Study Overview
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Brief Summary
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This study is a randomized, multicenter, multivendor, controlled, diagnostic superiority trial to compare digital breast tomosynthesis plus synthesized 2D mammograms (DBT+s2D) versus standard 2D full-field digital mammography (2D-FFDM) regarding the effectiveness as screening modality.

Detailed Description
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The primary objective of the study is to evaluate whether digital breast tomosynthesis plus synthesized 2D mammograms leads to a relevant increase in the detection rate of screening-detected invasive cancers compared to 2D full-field digital mammography in routine screening according to the European Guidelines. Furthermore, the incidence rate of interval cancers within a 24 months interval after screening will be compared between both study arms in order to investigate the potential for overdiagnosis. According to the pre-defined order of both primary endpoints and the primary objective of the study in the planning phase, the initial sample size calculation was based solely on the first primary endpoint (invasive breast cancer detection rate). Given the increasing national and international attention of interval cancers to assess the impact of potential overdiagnosis caused by tomosynthesis, we have planned a sample size increase from 80,000 to 120,000 study participants to achieve a reasonable statistical power for the evaluation of both primary endpoints. The revised sample size calculation was carried out without knowledge of the data from the currently recruiting TOSYMA study, i.e. all planning assumptions were based on external data that do not belong to the ongoing study.

Official Title
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Prospective Randomized Comparison of Digital Breast Tomosynthesis Plus Synthesized Images Versus Standard Full-field Digital Mammography in Population-based Screening (TOSYMA)

Conditions
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Breast Cancer Screening

Intervention / Treatment
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* Diagnostic Test: DBT+s2D
* Diagnostic Test: 2D-FFDM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women eligible to participate in the National Mammography Screening Program of Germany Informed decision for mammography screening Written informed consent No prior participation in the TOSYMA trial Exclusion Criteria: Breast cancer up to 5 years prior to study invitation Previous mammography examination < 12 months, Breast implants

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 69 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
Interventional Model Description: Participants will be randomized to either Digital Breast Tomosynthesis plus synthesized 2D mammograms (DBT+s2D) or 2D Full-Field Digital Mammography (2D-FFDM)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DBT+s2D<br>Digital breast tomosynthesis plus synthesized 2D mammograms | Diagnostic Test: DBT+s2D<br>* Digital breast tomosynthesis plus synthesized 2D mammograms<br>|
| Active Comparator: 2D-FFDM<br>2D full-field digital mammography | Diagnostic Test: 2D-FFDM<br>* 2D full-field digital mammography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of invasive breast cancers | Number of women with screening-detected invasive breast cancer divided by the number of all women screened. A screening-detected breast cancer is classified as invasive carcinoma if the pT category (pathological tumor size) of the TNM classification falls into one of the following categories: pT1mic, pT1a, pT1b, pT1c, pT1, pT2, pT3, pT4a, pT4b, pT4c, pT4d, pT4, pTX (for evaluation purpose pTX defines histologically approved invasive breast cancer with missing tumor diameter) or the final pathological categorization has been done after neoadjuvant therapy (ypT), implying an invasive cancer prior to therapy. | Routine screening visit | 
| Cumulative 24 months incidence of interval cancers | The 24 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 24 months interval after a negative screening examination divided by the number of all women with a negative screening result. | 24 months after routine screening visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of ductal carcinoma in situ (DCIS) | Number of women with screening-detected ductal carcinoma in situ (if the pT category of the TNM classification falls into the category pTis) divided by the number of all women screened. | Routine screening visit | 
| Detection rate of tumor category pT1 | Number of women with screening-detected invasive breast cancers of the category pT1 divided by the number of all women screened. A screening-detected breast cancer is classified as breast cancer of tumor category pT1 if tumor size is ≤ 20 mm in greatest dimension and the respective pT subcategory of the pTNM classification is one of the following: pT1mic, pT1a, pT1b, pT1c, pT1. | Routine screening visit | 
| Recall rate for further assessment | Number of women with recalls for further assessment divided by the number of all women screened. | Routine Screening Visit | 
| Positive predictive value of recall for further assessment (PPV1) | Number of women with screening-detected malignancies (ductal carcinoma in situ or invasive breast cancer) divided by the number of women with recalls for further assessment. | Routine screening visit | 
| Cumulative 12 months incidence of interval cancers | The 12 months incidence of interval cancers is defined as the number of women that develop a ductal carcinoma in situ or an invasive breast cancer in the 12 months interval after a negative screening examination divided by the number of all women with a negative screening result. | 12 months after routine screening visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Population-based Screening, Digital Breast Tomosynthesis plus synthesized Mammography, Reconstructed Mammography, Full-Field Digital Mammography (FFDM), Multicentric Randomized Controlled Trial, Diagnostic Performance, Recall Rate, Interval Cancer