Breast CancerDENSE-2NCT06636370
Supplemental Screening for Women With Extremely Dense Breast Tissue: the DENSE-2 Trial
A study testing Contrast-enhanced mammography (CEM) and Abbreviated MRI (AB-MRI) in people with Breast Cancer, run by C.H. van Gils at 1 site in Netherlands.
Trial summary
Women with extremely dense breasts (nearly all glandular and connective tissue, little fatty tissue) have a 3-6 times higher risk of breast cancer than women with very low breast density. Moreover, due to the masking effect of the dense tissue, any breast tumours present are more difficult to detect in these women. Read more about this study
- Who is it for?
- Ages 49 to 72 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Contrast-enhanced mammography (CEM) and Abbreviated MRI (AB-MRI)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36,000 participants
- Where
- 1 siteNetherlands
- Study dates
- 11 Nov 2024to 1 Sep 2031
- 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 49 to 72 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participant in the Dutch population-based breast cancer screening program with a negative mammography result (BI-RADS classification 1 or 2).
- Extremely dense breast tissue (assessed with Quantra software, category D).
- Age between 49-72 years (women are invited to the Dutch screening program in the year they turn 50, so the minimum age is 49 years. The maximum age for inclusion is 72 years to ensure that women can still participate in a second round of supplemental screening).
- Living in the service area (travel distance of up to 60 km) of the 15 participating hospitals.
- Absence of breast implants (Quantra cannot provide an accurate density determination for breasts with implants).
- No objection to data sharing.
- Not a participant in the DENSE trial or STREAM trial (participants in the DENSE and STREAM trials are known to the Dutch screening organization).
Who cannot join
- The additional exclusion criteria for the intervention arms are checked after randomization and recruitment (this order is due to the pre-randomization design):
- Presence of in-body metals (only for AB-MRI, this involves specific metals and is asked by telephone).
- Previous allergic reaction to the provided contrast agent.
- Renal insufficiency (glomerular filtration rate <30 ml/min) (only for CEM, is checked for with questionnaire I and possibly renal function measurement).
- Severe claustrophobia (only for AB-MRI).
- Severe obesity (weight >150 kg) (only for AB-MRI).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Evelyn Monninkhof, Dr. contact
Netherlands1 site, 1 recruiting
- Recruiting
UMC Utrecht
Utrecht
Sophie van Grinsven, Msc., 0031-88-7568181, dense-2@umcutrecht.nl
About this study
Official title: Contrast-enhanced Mammography and Abbreviated MRI as Supplemental Screening Modalities for Women Aged 50-75 With Extremely Dense Breast Tissue: the DENSE-2 Trial
Women with extremely dense breasts (nearly all glandular and connective tissue, little fatty tissue) have a 3-6 times higher risk of breast cancer than women with very low breast density. Moreover, due to the masking effect of the dense tissue, any breast tumours present are more difficult to detect in these women. With the results of the DENSE trial, the investigators showed that among women with extremely dense breasts, a combination of MRI and mammography could detect tumours earlier than mammography only. As the implementation of MRI in the screening program induces considerable costs and capacity requirements, the Dutch Ministry of Health would like to investigate whether cheaper and acceptable alternatives can be implemented more easily. In the DENSE-2 study, proposed here, we will investigate contrast-enhanced mammography and an abbreviated form of MRI as alternatives, in a large-scale randomized trial, within the current population-based screening program.
Read the detailed description
Women with extremely dense breast tissue have a higher risk of developing breast cancer and at the same time, mammography has limited value for these women. Currently, these women are not offered supplemental screening. Therefore, the investigators of the DENSE-2 trial will study supplemental CEM and AB-MRI screening in women with extremely dense breast tissue within the population-based breast cancer screening program because these modalities are expected to have higher diagnostic accuracy than tomosynthesis and ultrasound. In addition, these modalities are expected to be less expensive and require less capacity than a full MRI protocol as examined in the DENSE trial. For both CEM and AB-MRI, no results are currently available from a prospective screening study. The DENSE-2 trial is a randomized controlled trial comparing two intervention arms (CEM [intervention arm A] and abbreviated MRI [intervention arm B]) each with mammography [control arm C].
- Conditions
- Breast Cancer
- Being tested
- Contrast-enhanced mammography (CEM), Abbreviated MRI (AB-MRI)
- Keywords
- breast cancer screening, extremely dense breasts, early detection, contrast-enhanced mammography, abbreviated MRI
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Contrast-enhanced mammography (CEM)Diagnostic test
This intervention group receives supplemental screening with CEM after a negative screening result within the Dutch National Breast Cancer Screening program
Abbreviated MRI (AB-MRI)Diagnostic test
This intervention group receives supplemental screening with AB-MRI after a negative screening result within the Dutch National Breast Cancer Screening program
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | This group receives biennial mammography only within the current Dutch National Breast Cancer Screening program. This group will not be informed about the study (pre-randomisation design) |
| Contrast-enhanced Mammography (CEM) | Experimental | This group receives supplemental screening with CEM after a negative mammography result in the Dutch National Breast Cancer screening program Receives: Diagnostic Test: Contrast-enhanced mammography (CEM) |
| Abbreviated MRI (AB-MRI) | Experimental | This group receives supplemental screening with AB-MRI after a negative mammography result in the Dutch National Breast Cancer Screening program Receives: Diagnostic Test: Abbreviated MRI (AB-MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interval Cancer Rate
Measured as a breast cancer diagnosed in between two screening rounds
Measured: 0 - 3 year
Secondary outcomes (19)
Advanced Cancer detectio Advanced Cancer rate
Advanced cancer is defined as TNM stage II or higher
Measured: 0 - 3 year
Cancer detection rate
The number of breast cancers detected by CEM or AB-MRI
Measured: 0 - 3 year
False positive rate
The number with a false positive result after CEM or AB-MRI
Measured: 0-5 year
Participant experience with CEM - 1
screen-specific item questionnaire (SSI)
Measured: 0-5 year
Participant experience with CEM - 2
Self-developed questionnaire
Measured: 0-5 year
Participant experience with CEM - 3
Focus group interviews
Measured: 0-5 year
Participant experience with AB-MRI - 1
screen-specific item questionnaire (SSI)
Measured: 0-5 year
Participant experience with AB-MRI - 2
Self-developed questionnaire
Measured: 0-5 year
Participant experience with AB-MRI - 3
Focus group interviews
Measured: 0-5 year
Health-professional experience with CEM
Self-developed questionnaire
Measured: 0-5 year
Health-professional experience with AB-MRI
Self-developed questionnaire
Measured: 0-5 year
Estimated rate of overdiagnosis
Simulation with the MISCAN software
Measured: 0-5 years
Cost-effectiveness
Simulation with the MISCAN software
Measured: 0-5 year
Breast tumor size
mm
Measured: 0-5 years
Breast tumor stage
TNM classification
Measured: 0-5 years
Positive Predictive Value (PPV)
Using the histological diagnosis as the reference test
Measured: 0-5 year
Biopsy rate
Per 1000 women screened with one of the modalities
Measured: 0-5 year
Referral rate
Per 1000 women screened per screening modality
Measured: 0-5 years
Mortality rate
Simulation with MISCAN software
Measured: 0-5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2024
- Study start11 Nov 2024
- Primary completion31 Dec 2029 (estimated)
- Study completion1 Sep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies 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
- Masking
- None (open label)
- Enrolment
- 36,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- C.H. van Gils
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen, Ziekenhuisgroep Twente, Radboud University Medical Center, Rijnstate Hospital, Zuyderland Medical Centre, Maastricht University Medical Center, Elisabeth-TweeSteden Ziekenhuis, Catharina Ziekenhuis Eindhoven, Jeroen Bosch Hospital, Erasmus Medical Center, Albert Schweitzer Hospital, St. Antonius Hospital, Antoni van Leeuwenhoek Hospital, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Bevolkingsonderzoek Nederland, Borstkankervereniging Nederland
- Responsible party
- Sponsor-investigator, C.H. van Gils, UMC Utrecht
- Investigators
- Carla van Gils, Prof., Principal investigator, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06636370
- Sponsor's protocol ID
- 05550412310002
- Other IDs
- Nr. 2024/09
- Acronym
- DENSE-2
- Status last verified
- May 2026
- First submitted
- 3 Oct 2024
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
van Grinsven SEL, Monninkhof EM, Mann RM, Lobbes MBI, Broeders MJM, van Ravesteyn NT, Bluekens AMJ, van Diest PJ, Dorrius MD, Duvivier KM, Gielens MPM, de Jong MDF, Kock MCJM, Loo CE, Meeuwis C, de Monye C, van Nijnatten TJA, Pijnappel RM, Trap-de Jong JP, Veltman J, Veldhuis WB, van Gils CH; DENSE-2 Trial Study Group; DENSE-2 trial study group. Supplemental Breast Cancer Screening with Contrast-enhanced Mammography or Abbreviated MRI for Extremely Dense Breasts: The DENSE-2 Trial. Radiology. 2026 Oct;321(1):e260333. doi: 10.1148/radiol.260333.
PubMed 42867374
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contrast-enhanced Mammography and Abbreviated MRI as Supplemental Screening Modalities for Women Aged 50-75 With Extremely Dense Breast Tissue: the DENSE-2 Trial
- ClinicalTrials.gov ID
- NCT06636370
- Acronym / sponsor ID
- DENSE-2 / 05550412310002
- Conditions
- Breast Cancer
- Keywords
- breast cancer screening, extremely dense breasts, early detection, contrast-enhanced mammography, abbreviated MRI
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36,000 participants (estimated)
- Lead sponsor
- C.H. van GilsUniversity, hospital or other
- Collaborators
- University Medical Center Groningen, Ziekenhuisgroep Twente, Radboud University Medical Center, Rijnstate Hospital, Zuyderland Medical Centre, Maastricht University Medical Center, Elisabeth-TweeSteden Ziekenhuis, Catharina Ziekenhuis Eindhoven, Jeroen Bosch Hospital, Erasmus Medical Center, Albert Schweitzer Hospital, St. Antonius Hospital, Antoni van Leeuwenhoek Hospital, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Bevolkingsonderzoek Nederland, Borstkankervereniging Nederland
- Study start
- 11 Nov 2024 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 1 Sep 2031 (estimated)
- First posted
- 10 Oct 2024 (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.
Women with extremely dense breasts (nearly all glandular and connective tissue, little fatty tissue) have a 3-6 times higher risk of breast cancer than women with very low breast density. Moreover, due to the masking effect of the dense tissue, any breast tumours present are more difficult to detect in these women. With the results of the DENSE trial, the investigators showed that among women with extremely dense breasts, a combination of MRI and mammography could detect tumours earlier than mammography only. As the implementation of MRI in the screening program induces considerable costs and capacity requirements, the Dutch Ministry of Health would like to investigate whether cheaper and acceptable alternatives can be implemented more easily. In the DENSE-2 study, proposed here, we will investigate contrast-enhanced mammography and an abbreviated form of MRI as alternatives, in a large-scale randomized trial, within the current population-based screening program.
Detailed description
Women with extremely dense breast tissue have a higher risk of developing breast cancer and at the same time, mammography has limited value for these women. Currently, these women are not offered supplemental screening. Therefore, the investigators of the DENSE-2 trial will study supplemental CEM and AB-MRI screening in women with extremely dense breast tissue within the population-based breast cancer screening program because these modalities are expected to have higher diagnostic accuracy than tomosynthesis and ultrasound. In addition, these modalities are expected to be less expensive and require less capacity than a full MRI protocol as examined in the DENSE trial. For both CEM and AB-MRI, no results are currently available from a prospective screening study. The DENSE-2 trial is a randomized controlled trial comparing two intervention arms (CEM [intervention arm A] and abbreviated MRI [intervention arm B]) each with mammography [control arm C].
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –This group receives biennial mammography only within the current Dutch National Breast Cancer Screening program. This group will not be informed about the study (pre-randomisation design) |
| Contrast-enhanced Mammography (CEM) | Experimental | Diagnostic Test: Contrast-enhanced mammography (CEM)This group receives supplemental screening with CEM after a negative mammography result in the Dutch National Breast Cancer screening program |
| Abbreviated MRI (AB-MRI) | Experimental | Diagnostic Test: Abbreviated MRI (AB-MRI)This group receives supplemental screening with AB-MRI after a negative mammography result in the Dutch National Breast Cancer Screening program |
Who may qualify
- Ages
- 49 to 72 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Participant in the Dutch population-based breast cancer screening program with a negative mammography result (BI-RADS classification 1 or 2).
- Extremely dense breast tissue (assessed with Quantra software, category D).
- Age between 49-72 years (women are invited to the Dutch screening program in the year they turn 50, so the minimum age is 49 years. The maximum age for inclusion is 72 years to ensure that women can still participate in a second round of supplemental screening).
- Living in the service area (travel distance of up to 60 km) of the 15 participating hospitals.
- Absence of breast implants (Quantra cannot provide an accurate density determination for breasts with implants).
Key exclusion criteria (6 listed)
- The additional exclusion criteria for the intervention arms are checked after randomization and recruitment (this order is due to the pre-randomization design):
- Presence of in-body metals (only for AB-MRI, this involves specific metals and is asked by telephone).
- Previous allergic reaction to the provided contrast agent.
- Renal insufficiency (glomerular filtration rate <30 ml/min) (only for CEM, is checked for with questionnaire I and possibly renal function measurement).
- Severe claustrophobia (only for AB-MRI).
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 |
|---|---|---|
| Contrast-enhanced mammography (CEM)This intervention group receives supplemental screening with CEM after a negative screening result within the Dutch National Breast Cancer Screening program | Diagnostic test | Contrast-enhanced Mammography (CEM) |
| Abbreviated MRI (AB-MRI)This intervention group receives supplemental screening with AB-MRI after a negative screening result within the Dutch National Breast Cancer Screening program | Diagnostic test | Abbreviated MRI (AB-MRI) |
Primary outcome
Interval Cancer Rate
Time frame: 0 - 3 year
Measured as a breast cancer diagnosed in between two screening rounds
19 secondary outcomes
Advanced Cancer detectio Advanced Cancer rate
Time frame: 0 - 3 year
Cancer detection rate
Time frame: 0 - 3 year
False positive rate
Time frame: 0-5 year
Participant experience with CEM - 1
Time frame: 0-5 year
Participant experience with CEM - 2
Time frame: 0-5 year
Participant experience with CEM - 3
Time frame: 0-5 year
Participant experience with AB-MRI - 1
Time frame: 0-5 year
Participant experience with AB-MRI - 2
Time frame: 0-5 year
Participant experience with AB-MRI - 3
Time frame: 0-5 year
Health-professional experience with CEM
Time frame: 0-5 year
Health-professional experience with AB-MRI
Time frame: 0-5 year
Estimated rate of overdiagnosis
Time frame: 0-5 years
Cost-effectiveness
Time frame: 0-5 year
Breast tumor size
Time frame: 0-5 years
Breast tumor stage
Time frame: 0-5 years
Positive Predictive Value (PPV)
Time frame: 0-5 year
Biopsy rate
Time frame: 0-5 year
Referral rate
Time frame: 0-5 years
Mortality rate
Time frame: 0-5 year
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 11 May 2026.
- Derived from this study: PubMed 42867374van Grinsven SEL, Monninkhof EM, Mann RM, Lobbes MBI, Broeders MJM, van Ravesteyn NT, Bluekens AMJ, van Diest PJ, Dorrius MD, Duvivier KM, Gielens MPM, de Jong MDF, Kock MCJM, Loo CE, Meeuwis C, de Monye C, van Nijnatten TJA, Pijnappel RM, Trap-de Jong JP, Veltman J, Veldhuis WB, van Gils CH; DENSE-2 Trial Study Group; DENSE-2 trial study group. Supplemental Breast Cancer Screening with Contrast-enhanced Mammography or Abbreviated MRI for Extremely Dense Breasts: The DENSE-2 Trial. Radiology. 2026 Oct;321(1):e260333. doi: 10.1148/radiol.260333.
- 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.
Evelyn Monninkhof, Dr. contact
Carla van Gils, Prof. principal investigator
UMC Utrecht
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Contrast-enhanced mammography (CEM) and Abbreviated MRI (AB-MRI) in people with Breast Cancer, run by C.H. van Gils at 1 site in Netherlands.
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 7 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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?
Contact Carla van Gils, Prof (0031-88-7568181, dense-2@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interval Cancer Rate (time frame: 0 - 3 year). 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 NCT06636370, which also lists 1 linked publication.
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 11 May 2026.