The Tomosynthesis Trial in Bergen - Part 2 (To-Be 2)

• ClinicalTrials.gov Identifier: NCT03669926
• Recruitment Status: Recruiting
• First Posted: September 13, 2018
• Last Update Posted: September 14, 2018
• Sponsor: Cancer Registry of Norway
• Collaborators: Haukeland University Hospital; University of Oslo; Norwegian Cancer Society
• Information provided by (Responsible Party): Cancer Registry of Norway

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Radiation: Digital Breast Tomosynthesis+synthetic mammography	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 32400 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Digital Breast Tomosynthesis - The Future Screening Tool for Breast Cancer?
• Actual Study Start Date: January 1, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
DBT+SM; 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; Two-view tomosynthesis performed with GE Senographe Pristina.; Other Name: DBT+SM

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 48 months from start up of the trial ]
   Rate of screening detected breast cancer, among those screened

Secondary Outcome Measures :

1. 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. [ Time Frame: 48 months from start up of the trial ]
   Rate of recalled women due to mammographic findings, among those screened
2. 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. [ Time Frame: 48 months from start up of the trial ]
   Rate of breast cancer cases among those recalled
3. 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. [ Time Frame: 48 months from start up of the trial ]
   Distribution of characteristics among the women diagnosed with breast cancer
4. 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. [ Time Frame: 48 months from start up of the trial ]
   Rates and prognostic and predictive tumor characteristics of interval cancer among women screened in To-Be 1, stratified by mammographic density.
5. Rate of missed and true screen-detected and interval breast cancer in mammographic screening with DBT+SM versus DM. [ Time Frame: 24-48 month after start up of the trial ]
   Retrospective review of prior and actual mammograms from women with interval and screen-detected breast cancers detected in To-Be 1 and 2, respectively.
6. Economical aspects of continuous use of DBT+SM [ Time Frame: 48 months from start up of the trial ]
   Estimation of the financial impact of running a screening program with DBT+SM in an everyday setting.
7. Comparing interpretation times to investigate possible learning effects when reading DBT+SM in two consecutive screening rounds [ Time Frame: 48 months from start up of the trial ]
   Evaluation of difference in interpretation time for subsequent versus prevalent DBT+SM screens
8. Assessing degree of experienced and expected pain in DBT+SM screening by compression pressure using questionnaire [ Time Frame: 6 to 48 months after start up of the trial ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 48 Years to 71 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Only women are invited to breast cancer screening in BreastScreenn Norway.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Written, informed consent to participation

Exclusion Criteria:

• No written, informed consent to participation
• Breast implants

Contacts and Locations

Contacts

Contact: Solveig Hofvind, Professor; +4722928828; solveig.hofvind@kreftregisteret.no

Contact: Åsne S Holen, MSc; +4722928760; asne.holen@kreftregisteret.no

Locations

Norway

Cancer Registry of Norway; Recruiting

Oslo, Norway, 0379

Contact: Solveig Hofvind +47 22928828 solveig.hofvind@kreftregisteret.no

Contact: Åsne Holen +47 22928760 asne.holen@kreftregisteret.no

Sponsors and Collaborators

Cancer Registry of Norway

Haukeland University Hospital

University of Oslo

Norwegian Cancer Society

Investigators

• Principal Investigator: Solveig Hofvind, Professor; Cancer Registry of Norway

More Information

• Responsible Party: Cancer Registry of Norway
• ClinicalTrials.gov Identifier: NCT03669926 History of Changes
• Other Study ID Numbers: 17/209; 190184-2017 ( Other Grant/Funding Number: Norwegian Cancer Society )
• First Posted: September 13, 2018
• Last Update Posted: September 14, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: We will not share the data outside the project group

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cancer Registry of Norway:

Diagnostic Imaging; Mammography; Tomosynthesis; Breast cancer screening; Subsequent screening; Cancer detection; Cost effectiveness; Early performance measures; Interval cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases