The Tomosynthesis Trial in Bergen - Part 2

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to compare early performance measures and economic aspects of organized breast cancer screening for women screened using digital breast tomosynthesis+synthetic mammography (DBT+SM) to women with a prior DBT+SM or digital mammography (DM) from To-Be 1 (NCT02835625).

Detailed Description
-----------------
Digital breast tomosynthesis (DBT) is a new three-dimensional screening tool for breast cancer, claimed to be superior to standard two-dimensional (2D) digital mammography (DM) based on results of lower or similar recall rate, and a 30-50% higher rate of screen-detected breast cancer for DBT compared to DM. The Bergen Tomosynthesis Trial (To-Be) is a randomized controlled trial investigating whether DBT, including synthetic mammography (SM), is superior for breast cancer screening to DM (ClinicalTrials.gov Identifier: NCT02835625) - hereafter referred to as To-Be 1. The study is run as part of BreastScreen Norway (inviting women aged 50-69 to screening every two years). It started in October 2015 and finished recruitment in December 2017, after two years - one screening round - of data collection. Results from To-Be 1 will fill some of the knowledge gaps regarding DBT+SM in screening. However, running To-Be 1 and recent publications on the topic have identified additional challenges and new evidence gaps that are important to address before DBT can be considered for use in organized screening. Thus, the To-Be trail will be extended with five more year (To-Be 2), consisting of one additional screening round (two years) where all women in the study population are screened with DBT+SM with a three year follow-up. To investigate the effect of subsequent screening with DBT+SM all women attending mammography screening in Bergen in 2018 and 2019 will be screened with DBT+SM. To-Be 2 is a prospective cohort study targeting 32 000 women, and all women attending screening will be asked if they are willing to take part in the study after receiving written and oral information about the study. Women willing to participate in the study will sign an informed consent form. We expect a participation rate of 90%. The participating women will be screened with DBT+SM. Women not willing to participate in the study will be screened with DM, and not included in our study. Continuing To-Be 1 with To-Be 2 is the only opportunity to get information on women subsequently screened with DBT+SM, that have a prior DBT+SM or DM based on random allocation. This will also allow the investigators to analyze data on interval breast cancer among women screened with DBT+SM after DBT+SM and with DBT+SM after DM in To-Be 1 in 2020. The investigators aim to address the following topics and research questions: Part I: Early performance measures for screening with DBT+SM after DBT+SM, and DBT+SM after DM. Part II: Interval breast cancer following screening with DBT+SM versus DM, focusing on interval breast cancers identified among women screened in To-Be 1. Part III: Missed and true screen-detected and interval breast cancer in mammographic screening with DBT+SM versus DM. Part IV: Expected and experienced discomfort and pain in DBT+SM by compression force and pressure. Part V: Economic evaluation of continuous use of DBT.

Official Title
-----------------
Digital Breast Tomosynthesis - The Future Screening Tool for Breast Cancer?

Conditions
-----------------
Breast Neoplasms

Intervention / Treatment
-----------------
* Radiation: Digital Breast Tomosynthesis+synthetic mammography


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written, informed consent to participation Exclusion Criteria: No written, informed consent to participation Breast implants

Ages Eligible for Study
-----------------
Minimum Age: 48 Years
Maximum Age: 71 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: DBT+SM<br>Digital Breast Tomosynthesis+synthetic mammography (DBT+SM) All women are screened with DBT+SM. All examinations are independently double read. Consensus used to decide whether or not to recall. | Radiation: Digital Breast Tomosynthesis+synthetic mammography<br>* Two-view tomosynthesis performed with GE Senographe Pristina.<br>* Other names: DBT+SM;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare rates of screen detected breast cancer after subsequent screening with DBT+SM after DBT+SM versus screening with DBT+SM after prior DM, as performed in a population based screening program. | Rate of screening detected breast cancer, among those screened | 48 months from start up of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare recall rates after subsequent screening with DBT+SM after DBT+SM versus screening with DBT+SM after prior DM, as performed in a population based screening program. | Rate of recalled women due to mammographic findings, among those screened | 48 months from start up of the trial | 
| Positive predictive value of recalls after subsequent screening with DBT+SM after DBT+SM versus screening with DBT+SM after prior DM, as performed in a population based screening program. | Rate of breast cancer cases among those recalled | 48 months from start up of the trial | 
| Prognostic and predictive tumor characteristics for screening detected breast cancer after subsequent screening with DBT+SM after DBT+SM versus screening with DBT+SM after prior DM, as performed in a population based screening program. | Distribution of characteristics among the women diagnosed with breast cancer | 48 months from start up of the trial | 
| Rate of interval breast cancer following screening with DBT+SM after DBT+SM versus screening with DBT+SM after prior DM, as performed in a population based screening program. | Rates and prognostic and predictive tumor characteristics of interval cancer among women screened in To-Be 1, stratified by mammographic density. | 48 months from start up of the trial | 
| Rate of missed and true screen-detected and interval breast cancer in mammographic screening with DBT+SM versus DM. | Retrospective review of prior and actual mammograms from women with interval and screen-detected breast cancers detected in To-Be 1 and 2, respectively. | 24-48 month after start up of the trial | 
| Economical aspects of continuous use of DBT+SM | Estimation of the financial impact of running a screening program with DBT+SM in an everyday setting. | 48 months from start up of the trial | 
| Comparing interpretation times to investigate possible learning effects when reading DBT+SM in two consecutive screening rounds | Evaluation of difference in interpretation time for subsequent versus prevalent DBT+SM screens | 48 months from start up of the trial | 
| Assessing degree of experienced and expected pain in DBT+SM screening by compression pressure using questionnaire | Explore whether individualized, standardized compression pressure influences women's screening experiences using a numeric rating scale (0 No discomfort/pain to 10 Very much discomfort/pain). Drafting of the questionnaire is in progress. | 6 to 48 months after start up of the trial | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diagnostic Imaging, Mammography, Tomosynthesis, Breast cancer screening, Subsequent screening, Cancer detection, Cost effectiveness, Early performance measures, Interval cancer