Supplemental Screening for Women With Extremely Dense Breast Tissue: the DENSE-2 Trial (DENSE-2)

May 6, 2026 updated by: C.H. van Gils

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Control
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)
Experimental: Contrast-enhanced Mammography (CEM)
This group receives supplemental screening with CEM after a negative mammography result in the Dutch National Breast Cancer screening program
Diagnostic test: 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
Experimental: 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
Diagnostic test: 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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Interval Cancer Rate
Time Frame: 0 - 3 year
Measured as a breast cancer diagnosed in between two screening rounds
0 - 3 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cancer detection rate
Time Frame: 0 - 3 year
The number of breast cancers detected by CEM or AB-MRI
0 - 3 year
False positive rate
Time Frame: 0-5 year
The number with a false positive result after CEM or AB-MRI
0-5 year
Participant experience with CEM - 1
Time Frame: 0-5 year
screen-specific item questionnaire (SSI)
0-5 year
Participant experience with CEM - 2
Time Frame: 0-5 year
Self-developed questionnaire
0-5 year
Participant experience with CEM - 3
Time Frame: 0-5 year
Focus group interviews
0-5 year
Participant experience with AB-MRI - 1
Time Frame: 0-5 year
screen-specific item questionnaire (SSI)
0-5 year
Participant experience with AB-MRI - 2
Time Frame: 0-5 year
Self-developed questionnaire
0-5 year
Participant experience with AB-MRI - 3
Time Frame: 0-5 year
Focus group interviews
0-5 year
Health-professional experience with CEM
Time Frame: 0-5 year
Self-developed questionnaire
0-5 year
Health-professional experience with AB-MRI
Time Frame: 0-5 year
Self-developed questionnaire
0-5 year
Estimated rate of overdiagnosis
Time Frame: 0-5 years
Simulation with the MISCAN software
0-5 years
Cost-effectiveness
Time Frame: 0-5 year
Simulation with the MISCAN software
0-5 year
Breast tumor size
Time Frame: 0-5 years
mm
0-5 years
Breast tumor stage
Time Frame: 0-5 years
TNM classification
0-5 years
Positive Predictive Value (PPV)
Time Frame: 0-5 year
Using the histological diagnosis as the reference test
0-5 year
Biopsy rate
Time Frame: 0-5 year
Per 1000 women screened with one of the modalities
0-5 year
Referral rate
Time Frame: 0-5 years
Per 1000 women screened per screening modality
0-5 years
Mortality rate
Time Frame: 0-5 year
Simulation with MISCAN software
0-5 year
Advanced Cancer detectio Advanced Cancer rate
Time Frame: 0 - 3 year
Advanced cancer is defined as TNM stage II or higher
0 - 3 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
C.H. van Gils

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Radboud University Medical Center
University Medical Center Groningen
Maastricht University Medical Center
Erasmus Medical Center
Catharina Ziekenhuis Eindhoven
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
St. Antonius Hospital
Albert Schweitzer Hospital
Elisabeth-TweeSteden Ziekenhuis
Rijnstate Hospital
Ziekenhuisgroep Twente
Zuyderland Medical Centre
Antoni van Leeuwenhoek Hospital
Jeroen Bosch Hospital
Bevolkingsonderzoek Nederland
Borstkankervereniging Nederland

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carla van Gils, Prof., UMC Utrecht

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 11, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 10, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 05550412310002
  • Nr. 2024/09 (Other Identifier: Dutch Health Council)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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