Breast Cancer ScreeningTOSYMANCT03377036
Breast Cancer Screening: Digital Breast Tomosynthesis Versus Digital 2D Mammography
A study testing DBT+s2D and 2D-FFDM in people with Breast Cancer Screening, run by University Hospital Muenster at 21 sites in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 to 69 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer Screening
- What is being tested?
- DBT+s2D and 2D-FFDM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99,689 participants
- Where
- 21 sitesGermany
- Study dates
- 5 Jul 2018to 31 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 69 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Breast cancer up to 5 years prior to study invitation
- Previous mammography examination < 12 months,
- Breast implants
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Germany21 sites
Screening-Einheit Aachen-Düren-Heinsberg; Mammographie-Einheit Aachen
Aachen, North Rhine-Westphalia, 52062
Referenz-Screening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Ahlen
Ahlen, North Rhine-Westphalia, 59227
Screening-Einheit Köln rechtsrheinisch, Leverkusen, Rhein.-Berg. Kreis, Oberbergischer Kreis; Mammographie-Einheit Bergisch Gladbach
Bergisch Gladbach, North Rhine-Westphalia, 51429
Screening-Einheit Bielefeld, Gütersloh; Mammographie-Einheit Bielefeld
Bielefeld, North Rhine-Westphalia, 33062
Screening-Einheit Münster-Süd; Mammographie-Einheit Coesfeld
Coesfeld, North Rhine-Westphalia, 48653
Screening-Einheit Duisburg; Mammographie-Einheit Duisburg
Duisburg, North Rhine-Westphalia, 47057
Screening-Einheit Gelsenkirchen, Kreis Recklinghausen, Bottrop; Mammographie-Einheit Gelsenkirchen
Gelsenkirchen, North Rhine-Westphalia, 45894
Screening-Einheit Hannover; Mammographie-Einheit Hannover
Hanover, Lower Saxony, 30449
Screening-Einheit Minden-Lübbecke, Herford; Mammographie-Einheit Herford
Herford, North Rhine-Westphalia, 32052
Screening-Einheit Mönchengladbach, Krefeld, Viersen; Mammographie-Einheit Krefeld
Krefeld, North Rhine-Westphalia, 47805
Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Lippstadt
Lippstadt, North Rhine-Westphalia, 59555
Screening-Einheit Niedersachsen Nordost; Mammographie-Einheit Lüneburg
Lüneburg, Lower Saxony, 21337
Referenz-Screeening-Einheit Münster-Nord/Warendorf; Mammographie-Einheit Münster-Nord
Münster, North Rhine-Westphalia, 48143
Screening-Einheit Münster-Süd; Mammographie-Einheit Münster
Münster, North Rhine-Westphalia, 48153
Screening-Einheit Höxter, Paderborn, Soest; Mammographie-Einheit Paderborn
Paderborn, North Rhine-Westphalia, 33098
Screening-Einheit Märkischer Kreis, Hamm, Unna; Mammographie-Einheit Schwerte
Schwerte, North Rhine-Westphalia, 58239
Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Solingen-Mitte
Solingen, North Rhine-Westphalia, 42651
Screening-Einheit Niedersachsen Nord; Mammographie-Einheit Stade
Stade, Lower Saxony, 21680
Screening-Einheit Niedersachsen Mitte; Mammographie-Einheit Vechta
Vechta, Lower Saxony, 49377
Screening-Einheit Niedersachsen Nordwest; Mammographie-Einheit Wilhelmshaven
Wilhelmshaven, Lower Saxony, 26382
Screening-Einheit Raum Bergisch Land/Kreis Mettmann; Mammographie-Einheit Wuppertal-Elberfeld
Wuppertal, North Rhine-Westphalia, 42109
About this study
Official title: Prospective Randomized Comparison of Digital Breast Tomosynthesis Plus Synthesized Images Versus Standard Full-field Digital Mammography in Population-based Screening (TOSYMA)
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.
Read the detailed description
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.
- Conditions
- Breast Cancer Screening
- Being tested
- DBT+s2D, 2D-FFDM
- Keywords
- 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
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DBT+s2DDiagnostic test
Digital breast tomosynthesis plus synthesized 2D mammograms
2D-FFDMDiagnostic test
2D full-field digital mammography
| Study group | Role | What they receive |
|---|---|---|
| DBT+s2D | Experimental | Digital breast tomosynthesis plus synthesized 2D mammograms Receives: Diagnostic Test: DBT+s2D |
| 2D-FFDM | Active comparator | 2D full-field digital mammography Receives: Diagnostic Test: 2D-FFDM |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 months after routine screening visit
Secondary outcomes (5)
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.
Measured: 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.
Measured: Routine screening visit
Recall rate for further assessment
Number of women with recalls for further assessment divided by the number of all women screened.
Measured: 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.
Measured: 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.
Measured: 12 months after routine screening visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start5 Jul 2018
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer ScreeningStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 99,689 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Sponsor
- Investigators
- Walter Heindel, MD, PhD, Principal investigator, University Clinic for Radiology, University of Muenster / University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03377036
- Sponsor's protocol ID
- UKM14_0016
- Other IDs
- HE1646/5-1 and HE1646/5-2
- Acronym
- TOSYMA
- Status last verified
- Jan 2026
- First submitted
- 13 Dec 2017
- Last updated
- 23 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Weigel S, Gerss J, Hense HW, Krischke M, Sommer A, Czwoydzinski J, Lenzen H, Kerschke L, Spieker K, Dickmaenken S, Baier S, Urban M, Hecht G, Heidinger O, Kieschke J, Heindel W. Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial. BMJ Open. 2018 May 14;8(5):e020475. doi: 10.1136/bmjopen-2017-020475.
PubMed 29764880Weigel S, Hense HW, Weyer-Elberich V, Czwoydzinski J, Decker T, Kajuter H, Oesterling F, Heilmann J, Stang A, Kieschke J, Wienbeck S, Stephan O, Baier S, Krischke M, Sommer A, Gerss J, Heindel W; TOSYMA Screening Trial Study Group. Invasive interval breast cancer rates after digital breast tomosynthesis plus synthesised mammography versus digital mammography screening (TOSYMA): 24-month follow-up of the multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2026 Oct 9:S1470-2045(26)00341-4. doi: 10.1016/S1470-2045(26)00341-4. Online ahead of print.
PubMed 42854706Weigel S, Hense HW, Weyer-Elberich V, Gerss J, Heindel W; TOSYMA Screening Trial Group. False-Positive Recall and False-Positive Biopsy Rates in Mammography Screening: A TOSYMA Trial Subanalysis. Radiology. 2025 Sep;316(3):e251014. doi: 10.1148/radiol.251014.
PubMed 40956160Weigel S, Heindel W, Hense HW, Decker T, Gerss J, Kerschke L; TOSYMA Screening Trial Study Group. Breast Density and Breast Cancer Screening with Digital Breast Tomosynthesis: A TOSYMA Trial Subanalysis. Radiology. 2023 Feb;306(2):e221006. doi: 10.1148/radiol.221006. Epub 2022 Oct 4.
PubMed 36194110Heindel W, Weigel S, Gerss J, Hense HW, Sommer A, Krischke M, Kerschke L; TOSYMA Screening Trial Study Group. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022 May;23(5):601-611. doi: 10.1016/S1470-2045(22)00194-2. Epub 2022 Apr 12.
PubMed 35427470
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomized Comparison of Digital Breast Tomosynthesis Plus Synthesized Images Versus Standard Full-field Digital Mammography in Population-based Screening (TOSYMA)
- ClinicalTrials.gov ID
- NCT03377036
- Acronym / sponsor ID
- TOSYMA / UKM14_0016
- Conditions
- Breast Cancer Screening
- Keywords
- 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
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 99,689 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- 5 Jul 2018 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 19 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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)
| Arm | Type | Receives |
|---|---|---|
| DBT+s2D | Experimental | Diagnostic Test: DBT+s2DDigital breast tomosynthesis plus synthesized 2D mammograms |
| 2D-FFDM | Active comparator | Diagnostic Test: 2D-FFDM2D full-field digital mammography |
Who may qualify
- Ages
- 50 to 69 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- Breast cancer up to 5 years prior to study invitation
- Previous mammography examination < 12 months,
- Breast implants
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DBT+s2DDigital breast tomosynthesis plus synthesized 2D mammograms | Diagnostic test | DBT+s2D |
| 2D-FFDM2D full-field digital mammography | Diagnostic test | 2D-FFDM |
Primary outcome
Detection rate of invasive breast cancers
Time frame: Routine screening visit
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.
Cumulative 24 months incidence of interval cancers
Time frame: 24 months after routine screening visit
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.
5 secondary outcomes
Detection rate of ductal carcinoma in situ (DCIS)
Time frame: Routine screening visit
Detection rate of tumor category pT1
Time frame: Routine screening visit
Recall rate for further assessment
Time frame: Routine Screening Visit
Positive predictive value of recall for further assessment (PPV1)
Time frame: Routine screening visit
Cumulative 12 months incidence of interval cancers
Time frame: 12 months after routine screening visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
- Background: PubMed 29764880Weigel S, Gerss J, Hense HW, Krischke M, Sommer A, Czwoydzinski J, Lenzen H, Kerschke L, Spieker K, Dickmaenken S, Baier S, Urban M, Hecht G, Heidinger O, Kieschke J, Heindel W. Digital breast tomosynthesis plus synthesised images versus standard full-field digital mammography in population-based screening (TOSYMA): protocol of a randomised controlled trial. BMJ Open. 2018 May 14;8(5):e020475. doi: 10.1136/bmjopen-2017-020475.
- Derived from this study: PubMed 42854706Weigel S, Hense HW, Weyer-Elberich V, Czwoydzinski J, Decker T, Kajuter H, Oesterling F, Heilmann J, Stang A, Kieschke J, Wienbeck S, Stephan O, Baier S, Krischke M, Sommer A, Gerss J, Heindel W; TOSYMA Screening Trial Study Group. Invasive interval breast cancer rates after digital breast tomosynthesis plus synthesised mammography versus digital mammography screening (TOSYMA): 24-month follow-up of the multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2026 Oct 9:S1470-2045(26)00341-4. doi: 10.1016/S1470-2045(26)00341-4. Online ahead of print.
- Derived from this study: PubMed 40956160Weigel S, Hense HW, Weyer-Elberich V, Gerss J, Heindel W; TOSYMA Screening Trial Group. False-Positive Recall and False-Positive Biopsy Rates in Mammography Screening: A TOSYMA Trial Subanalysis. Radiology. 2025 Sep;316(3):e251014. doi: 10.1148/radiol.251014.
- Derived from this study: PubMed 36194110Weigel S, Heindel W, Hense HW, Decker T, Gerss J, Kerschke L; TOSYMA Screening Trial Study Group. Breast Density and Breast Cancer Screening with Digital Breast Tomosynthesis: A TOSYMA Trial Subanalysis. Radiology. 2023 Feb;306(2):e221006. doi: 10.1148/radiol.221006. Epub 2022 Oct 4.
- Derived from this study: PubMed 35427470Heindel W, Weigel S, Gerss J, Hense HW, Sommer A, Krischke M, Kerschke L; TOSYMA Screening Trial Study Group. Digital breast tomosynthesis plus synthesised mammography versus digital screening mammography for the detection of invasive breast cancer (TOSYMA): a multicentre, open-label, randomised, controlled, superiority trial. Lancet Oncol. 2022 May;23(5):601-611. doi: 10.1016/S1470-2045(22)00194-2. Epub 2022 Apr 12.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter Heindel, MD, PhD principal investigator
University Clinic for Radiology, University of Muenster / University Hospital Muenster
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DBT+s2D and 2D-FFDM in people with Breast Cancer Screening, run by University Hospital Muenster at 21 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection rate of invasive breast cancers (time frame: Routine screening visit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03377036, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.