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

• ClinicalTrials.gov Identifier: NCT01315015
• Recruitment Status: Active, not recruiting
• First Posted: March 15, 2011
• Last Update Posted: November 7, 2022
• Sponsor: UMC Utrecht
• 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
• Information provided by (Responsible Party): C.H. van Gils, UMC Utrecht

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Other: Contrast enhanced breast MRI	Not Applicable

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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40373 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Screening
• Official Title: Breast Cancer Screening With MRI in Women Aged 50-75 Years With Extremely Dense Breast Tissue: the DENSE Trial
• Actual Study Start Date: November 2011
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Contrast enhanced breast MRI; The additional MRI will take place biennially after the regular screening mammogram for a study period of 6 years.	Other: Contrast enhanced breast MRI; Gadolinium contrast is administered as a bolus with a standard dose of 0.1 mL/kg followed by a saline flush of 30 mL.; Other Name: MR Mammography
No Intervention: Regular breast cancer screening; No further follow-up until next scheduled screening examination two years later (according to the current Dutch guideline).

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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) ]
   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.
2. 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 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.
3. 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 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.
4. 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 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.
5. 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 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.
6. 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 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.
7. The cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program [ Time Frame: 8 years ]
   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. The impact of MRI screening on quality of life will be assessed using standardized and validated questionnaires [ Time Frame: 8 years ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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)

Contacts and Locations

Locations

Netherlands

Jeroen Bosch Hospital

's-Hertogenbosch, Netherlands

Hospital Group Twente (ZGT)

Almelo, Netherlands

Antoni van Leeuwenhoek Hospital

Amsterdam, Netherlands

VU University Medical Center

Amsterdam, Netherlands

Albert Schweitzer Hospital

Dordrecht, Netherlands

Hospital Group Twente (ZGT)

Hengelo, Netherlands

Maastricht University Medical Center

Maastricht, Netherlands

Radboud University Medical Center

Nijmegen, Netherlands

UMC Utrecht

Utrecht, Netherlands

Sponsors and Collaborators

UMC Utrecht

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

Investigators

• Principal Investigator: Carla H van Gils, PhD; UMC Utrecht
• Principal Investigator: Wouter B Veldhuis, MD PhD; UMC Utrecht

  Study Documents (Full-Text)

Documents provided by C.H. van Gils, UMC Utrecht:

Study Protocol and Statistical Analysis Plan: Study protocol  [PDF] June 7, 2011

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

• Responsible Party: C.H. van Gils, Professor of Clinical Epidemiology of Cancer, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT01315015
• Other Study ID Numbers: UMCU DENSE; ZONMW-200320002-UMCU ( Other Grant/Funding Number: ZonMw ); Pink Ribbon-10074 ( Other Grant/Funding Number: Dutch Pink Ribbon / a Sister's hope ); BSP-DENSE ( Other Grant/Funding Number: Bayer HealthCare, Medical Care ); DCS-UU-2009-4348 ( Other Grant/Funding Number: Dutch Cancer Society ); DCS-UU-2014-6859 ( Other Grant/Funding Number: Dutch Cancer Society ); UMCU DENSE ( Other Grant/Funding Number: University Medical Center Utrecht )
• First Posted: March 15, 2011
• Last Update Posted: November 7, 2022
• Last Verified: November 2022

Keywords provided by C.H. van Gils, UMC Utrecht:

Breast cancer; Breast neoplasm; Magnetic Resonance Imaging; Breast density; Early detection of cancer; Cancer screening test; Secondary prevention

Additional relevant MeSH terms:

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