Breast CancerNCT01315015

Breast Cancer Screening With MRI in Women Aged 50-75 Years With Extremely Dense Breast Tissue: the DENSE Trial

A study testing Contrast enhanced breast MRI in people with Breast Cancer, run by UMC Utrecht at 9 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to determine the cost-effectiveness of biennial screening with mammography and MRI compared to mammography alone in women aged 50-75 years and who show > 75% mammographic density. Read more about this study

Who is it for?: Ages 50 to 75 years, women only
Conditions the study is for: Breast Cancer
What is being tested?: Contrast enhanced breast MRI
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40,373 participants
Where: 9 sitesNetherlands
Study dates: Nov 2011to Apr 2023
Phase: Interventional
Are there results?: None posted in the registry

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 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Dutch breast cancer screening participants, aged 50-75 years
> 75% mammographic density
Negative mammographic examination (BIRADS 1 or 2)

Who cannot join

Contraindications for MRI
The presence of intracorporeal metals
Adverse reaction to a (gadolinium-based) contrast agent in the past
Severely impaired renal function (GFR < 40 mL/min)
Pregnant or lactating women
Claustrophobia
Adiposity (> 150 kg)

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

Netherlands9 sites

Jeroen Bosch Hospital
's-Hertogenbosch
Hospital Group Twente (ZGT)
Almelo
Antoni van Leeuwenhoek Hospital
Amsterdam
VU University Medical Center
Amsterdam
Albert Schweitzer Hospital
Dordrecht
Hospital Group Twente (ZGT)
Hengelo
Maastricht University Medical Center
Maastricht
Radboud University Medical Center
Nijmegen
UMC Utrecht
Utrecht

Other trials in Netherlands

About this study

Read the detailed description

Women with very high mammographic density have a four to six fold higher breast cancer risk than women with low mammographic density. At the same time, the sensitivity of mammography is seriously impaired in women with high mammographic density, leading to many missed cases. Nevertheless, in the Netherlands this high risk group is currently screened between the age of 50 and 75 years with mammography only. MRI is likely to lead to better detection of breast tumors in women with high mammographic density, because it has a much higher sensitivity than mammography. The DENSE trial investigates the additional value of MRI for breast cancer screening in this risk group. Participants with extremely dense breasts (ACR4) and a negative mammogram are randomized to 'additional MRI' (n=7,237) versus 'current practice' (n=28,948).

Conditions: Breast Cancer
Being tested: Contrast enhanced breast MRI
Keywords: Breast cancer, Breast neoplasm, Magnetic Resonance Imaging, Breast density, Early detection of cancer, Cancer screening test, Secondary prevention
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 breast MRIOther
Also called MR Mammography
Gadolinium contrast is administered as a bolus with a standard dose of 0.1 mL/kg followed by a saline flush of 30 mL.

Study groups in NCT01315015
Study group	Role	What they receive
Contrast enhanced breast MRI	Experimental	The additional MRI will take place biennially after the regular screening mammogram for a study period of 6 years. Receives: Other: Contrast enhanced breast MRI
Regular breast cancer screening	No intervention	No further follow-up until next scheduled screening examination two years later (according to the current Dutch guideline).

What is being measured

The primary outcome is the main question the study is designed to answer.

The number of interval cancers will be compared between the MRI group and the control group
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.
Measured: 8 years (with an interim analysis every two years; time period between two screening rounds)

Secondary outcomes (8)

The number of MRI screen-detected tumors will be determined
The MRI examination will take place every two years (0, 2 and 4 years after inclusion). Given a two year recruitment period, the total study time will be 6 years.
Measured: 6 years (with an interim analysis every two years; time period between two screening rounds)
Tumor size, stage and grade distributions, including their histological and molecular subtypes, diagnosed in both study groups will be compared
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.
Measured: 8 years (with an interim analysis every two years; time period between two screening rounds)
The referral rate in the MRI study group will be determined
The MRI examination will take place every two years (0, 2 and 4 years after inclusion). Given a two year recruitment period, the total study time will be 6 years.
Measured: 6 years (with an interim analysis every two years; time period between two screening rounds)
The positive predictive value (and the amount of false-positive diagnoses) of MRI will be determined using the histological diagnosis as the reference test
The MRI examination will take place every two years (0, 2 and 4 years after inclusion). Given a two year recruitment period, the total study time will be 6 years.
Measured: 6 years (with an interim analysis every two years; time period between two screening rounds)
The number of biopsies per positive MRI will be determined
The MRI examination will take place every two years (0, 2 and 4 years after inclusion). Given a two year recruitment period, the total study time will be 6 years.
Measured: 6 years (with an interim analysis every two years; time period between two screening rounds)
The mortality rate in the MRI group will be compared with the control group using the MISCAN computer simulation program
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.
Measured: 8 years
The cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.
Measured: 8 years
The impact of MRI screening on quality of life will be assessed using standardized and validated questionnaires
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.
Measured: 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2011Apr 2023

First posted15 Mar 2011 (estimated)
Study startNov 2011
Primary completionApr 2023
Study completionApr 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by UMC UtrechtThe sponsor's other registered studies.
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: 40,373 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01315015
Sponsor's protocol ID: UMCU DENSE
Other IDs: ZONMW-200320002-UMCU, Pink Ribbon-10074, BSP-DENSE, DCS-UU-2009-4348, DCS-UU-2014-6859, UMCU DENSE
Status last verified: Apr 2025
First submitted: 14 Mar 2011
Last updated: 25 Apr 2025
Results posted: No
Data monitoring committee: Yes

Publications

van Grinsven SEL, Mann RM, Monninkhof EM, Duvivier K, de Jong MDF, de Koekkoek-Doll PK, Loo CE, Pijnappel RM, van der Sluijs R, Veltman J, van Gils CH, Veldhuis WB; DENSE Trial Study Group. Multireader Diagnostic Accuracy of Abbreviated Breast MRI for Screening Women with Extremely Dense Breasts. Radiology. 2025 May;315(2):e241233. doi: 10.1148/radiol.241233.
PubMed 40392091
Verburg E, van Gils CH, van der Velden BHM, Bakker MF, Pijnappel RM, Veldhuis WB, Gilhuijs KGA. Validation of Combined Deep Learning Triaging and Computer-Aided Diagnosis in 2901 Breast MRI Examinations From the Second Screening Round of the Dense Tissue and Early Breast Neoplasm Screening Trial. Invest Radiol. 2023 Apr 1;58(4):293-298. doi: 10.1097/RLI.0000000000000934. Epub 2022 Oct 17.
PubMed 36256783
Verburg E, van Gils CH, van der Velden BHM, Bakker MF, Pijnappel RM, Veldhuis WB, Gilhuijs KGA. Deep Learning for Automated Triaging of 4581 Breast MRI Examinations from the DENSE Trial. Radiology. 2022 Jan;302(1):29-36. doi: 10.1148/radiol.2021203960. Epub 2021 Oct 5.
PubMed 34609196
Veenhuizen SGA, de Lange SV, Bakker MF, Pijnappel RM, Mann RM, Monninkhof EM, Emaus MJ, de Koekkoek-Doll PK, Bisschops RHC, Lobbes MBI, de Jong MDF, Duvivier KM, Veltman J, Karssemeijer N, de Koning HJ, van Diest PJ, Mali WPTM, van den Bosch MAAJ, van Gils CH, Veldhuis WB; DENSE Trial Study Group. Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial. Radiology. 2021 May;299(2):278-286. doi: 10.1148/radiol.2021203633. Epub 2021 Mar 16.
PubMed 33724062
Bakker MF, de Lange SV, Pijnappel RM, Mann RM, Peeters PHM, Monninkhof EM, Emaus MJ, Loo CE, Bisschops RHC, Lobbes MBI, de Jong MDF, Duvivier KM, Veltman J, Karssemeijer N, de Koning HJ, van Diest PJ, Mali WPTM, van den Bosch MAAJ, Veldhuis WB, van Gils CH; DENSE Trial Study Group. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. N Engl J Med. 2019 Nov 28;381(22):2091-2102. doi: 10.1056/NEJMoa1903986.
PubMed 31774954
de Lange SV, Bakker MF, Monninkhof EM, Peeters PHM, de Koekkoek-Doll PK, Mann RM, Rutten MJCM, Bisschops RHC, Veltman J, Duvivier KM, Lobbes MBI, de Koning HJ, Karssemeijer N, Pijnappel RM, Veldhuis WB, van Gils CH. Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts. Clin Radiol. 2018 Aug;73(8):759.e1-759.e9. doi: 10.1016/j.crad.2018.04.002. Epub 2018 Jun 18.
PubMed 29759590

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Breast Cancer Screening With MRI in Women Aged 50-75 Years With Extremely Dense Breast Tissue: the DENSE Trial
ClinicalTrials.gov ID: NCT01315015
Acronym / sponsor ID: UMCU DENSE
Conditions: Breast Cancer
Keywords: Breast cancer, Breast neoplasm, Magnetic Resonance Imaging, Breast density, Early detection of cancer, Cancer screening test, Secondary prevention
Study type: Interventional
Recruitment status: Completed
Enrolment: 40,373 participants (actual)
Lead sponsor: UMC UtrechtUniversity, hospital or other
Collaborators: Dutch Breast Cancer Screening Organisations, Dutch Reference Centre for Screening, National Institute for Public Health and the Environment (RIVM), The Netherlands Cancer Institute, University Medical Center Nijmegen, Jeroen Bosch Ziekenhuis, Albert Schweitzer Hospital, Hospital Group Twente (ZGT), Amsterdam UMC, location VUmc, Maastricht University Medical Center, ZonMw: The Netherlands Organisation for Health Research and Development, Dutch Cancer Society, Pink Ribbon Inc., A Sister's Hope, Bayer, Stichting Kankerpreventie Midden-West, Volpara Solutions
Study start: Nov 2011 (actual)
Primary completion: Apr 2023 (actual)
Study completion: Apr 2023 (actual)
First posted: 15 Mar 2011 (estimated)
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.

Detailed description

Study design

Primary purpose: Screening
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Contrast enhanced breast MRI	Experimental	Other: Contrast enhanced breast MRIThe additional MRI will take place biennially after the regular screening mammogram for a study period of 6 years.
Regular breast cancer screening	No intervention	–No further follow-up until next scheduled screening examination two years later (according to the current Dutch guideline).

Who may qualify

Ages: 50 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Dutch breast cancer screening participants, aged 50-75 years
> 75% mammographic density
Negative mammographic examination (BIRADS 1 or 2)

Key exclusion criteria (7 listed)

Contraindications for MRI
The presence of intracorporeal metals
Adverse reaction to a (gadolinium-based) contrast agent in the past
Severely impaired renal function (GFR < 40 mL/min)
Pregnant or lactating women

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 breast MRIAlso: MR MammographyGadolinium contrast is administered as a bolus with a standard dose of 0.1 mL/kg followed by a saline flush of 30 mL.	Other	Contrast enhanced breast MRI

Primary outcome

The number of interval cancers will be compared between the MRI group and the control group
Time frame: 8 years (with an interim analysis every two years; time period between two screening rounds)
The intervention will be carried out for six years, i.e. 3 screening rounds. Given a two year recruitment period, the total study time will be 8 years.

8 secondary outcomes

The number of MRI screen-detected tumors will be determined
Time frame: 6 years (with an interim analysis every two years; time period between two screening rounds)
Tumor size, stage and grade distributions, including their histological and molecular subtypes, diagnosed in both study groups will be compared
Time frame: 8 years (with an interim analysis every two years; time period between two screening rounds)
The referral rate in the MRI study group will be determined
Time frame: 6 years (with an interim analysis every two years; time period between two screening rounds)
The positive predictive value (and the amount of false-positive diagnoses) of MRI will be determined using the histological diagnosis as the reference test
Time frame: 6 years (with an interim analysis every two years; time period between two screening rounds)
The number of biopsies per positive MRI will be determined
Time frame: 6 years (with an interim analysis every two years; time period between two screening rounds)
The mortality rate in the MRI group will be compared with the control group using the MISCAN computer simulation program
Time frame: 8 years
The cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program
Time frame: 8 years
The impact of MRI screening on quality of life will be assessed using standardized and validated questionnaires
Time frame: 8 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2025.
Derived from this study: PubMed 40392091van Grinsven SEL, Mann RM, Monninkhof EM, Duvivier K, de Jong MDF, de Koekkoek-Doll PK, Loo CE, Pijnappel RM, van der Sluijs R, Veltman J, van Gils CH, Veldhuis WB; DENSE Trial Study Group. Multireader Diagnostic Accuracy of Abbreviated Breast MRI for Screening Women with Extremely Dense Breasts. Radiology. 2025 May;315(2):e241233. doi: 10.1148/radiol.241233.
Derived from this study: PubMed 36256783Verburg E, van Gils CH, van der Velden BHM, Bakker MF, Pijnappel RM, Veldhuis WB, Gilhuijs KGA. Validation of Combined Deep Learning Triaging and Computer-Aided Diagnosis in 2901 Breast MRI Examinations From the Second Screening Round of the Dense Tissue and Early Breast Neoplasm Screening Trial. Invest Radiol. 2023 Apr 1;58(4):293-298. doi: 10.1097/RLI.0000000000000934. Epub 2022 Oct 17.
Derived from this study: PubMed 34609196Verburg E, van Gils CH, van der Velden BHM, Bakker MF, Pijnappel RM, Veldhuis WB, Gilhuijs KGA. Deep Learning for Automated Triaging of 4581 Breast MRI Examinations from the DENSE Trial. Radiology. 2022 Jan;302(1):29-36. doi: 10.1148/radiol.2021203960. Epub 2021 Oct 5.
Derived from this study: PubMed 33724062Veenhuizen SGA, de Lange SV, Bakker MF, Pijnappel RM, Mann RM, Monninkhof EM, Emaus MJ, de Koekkoek-Doll PK, Bisschops RHC, Lobbes MBI, de Jong MDF, Duvivier KM, Veltman J, Karssemeijer N, de Koning HJ, van Diest PJ, Mali WPTM, van den Bosch MAAJ, van Gils CH, Veldhuis WB; DENSE Trial Study Group. Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial. Radiology. 2021 May;299(2):278-286. doi: 10.1148/radiol.2021203633. Epub 2021 Mar 16.
Derived from this study: PubMed 31774954Bakker MF, de Lange SV, Pijnappel RM, Mann RM, Peeters PHM, Monninkhof EM, Emaus MJ, Loo CE, Bisschops RHC, Lobbes MBI, de Jong MDF, Duvivier KM, Veltman J, Karssemeijer N, de Koning HJ, van Diest PJ, Mali WPTM, van den Bosch MAAJ, Veldhuis WB, van Gils CH; DENSE Trial Study Group. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. N Engl J Med. 2019 Nov 28;381(22):2091-2102. doi: 10.1056/NEJMoa1903986.
Derived from this study: PubMed 29759590de Lange SV, Bakker MF, Monninkhof EM, Peeters PHM, de Koekkoek-Doll PK, Mann RM, Rutten MJCM, Bisschops RHC, Veltman J, Duvivier KM, Lobbes MBI, de Koning HJ, Karssemeijer N, Pijnappel RM, Veldhuis WB, van Gils CH. Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts. Clin Radiol. 2018 Aug;73(8):759.e1-759.e9. doi: 10.1016/j.crad.2018.04.002. Epub 2018 Jun 18.
Click here for more information about this study (website in Dutch language).Link provided by the sponsor.

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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.

Carla H van Gils, PhD principal investigator

UMC Utrecht

Wouter B Veldhuis, MD PhD principal investigator

UMC Utrecht

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Contrast enhanced breast MRI in people with Breast Cancer, run by UMC Utrecht at 9 sites 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 3 inclusion and 7 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: finished, as of the sponsor's last update on 25 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

The number of interval cancers will be compared between the MRI group and the control group (time frame: 8 years (with an interim analysis every two years; time period between two screening rounds)). 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 NCT01315015, which also lists 6 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 25 Apr 2025.