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

This study is enrolling participants by invitation only.
Sponsor:
Collaborators:
Dutch Breast Cancer Screening Organisations
Dutch Reference Centre for Screening
National Institute for Public Health and the Environment
Antoni van Leeuwenhoek Hospital
University Medical Center Nijmegen
Jeroen Bosch Hospital
Albert Schweitzer Hospital
Hospital Group Twente (ZGT)
VU University Medical Center
Maastricht University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Cancer Society
Dutch Pink Ribbon
A sister's hope
Bayer HealthCare, Medical Care
Stichting Kankerpreventie Midden-West
Matakina
Information provided by (Responsible Party):
C.H. van Gils, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01315015
First received: March 14, 2011
Last updated: August 2, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Breast Cancer
Other: Contrast enhanced breast MRI
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • The mortality rate in the MRI group will be compared with the control group using the MISCAN computer simulation program [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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.

  • The cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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.

  • The impact of MRI screening on quality of life will be assessed using standardized and validated questionnaires [ Time Frame: 8 years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 36185
Study Start Date: November 2011
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

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).

  Eligibility

Ages Eligible for Study:   49 Years to 75 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01315015

Locations
Netherlands
Jeroen Bosch Hospital
's-Hertogenbosch, Netherlands
Hospital Group Twente (ZGT)
Almelo and Hengelo, Netherlands
VU University Medical Center
Amsterdam, Netherlands
Antoni van Leeuwenhoek Hospital
Amsterdam, Netherlands
Albert Schweitzer Hospital
Dordrecht, 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
Antoni van Leeuwenhoek Hospital
University Medical Center Nijmegen
Jeroen Bosch Hospital
Albert Schweitzer Hospital
Hospital Group Twente (ZGT)
VU University Medical Center
Maastricht University Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Dutch Cancer Society
Dutch Pink Ribbon
A sister's hope
Bayer HealthCare, Medical Care
Stichting Kankerpreventie Midden-West
Matakina
Investigators
Principal Investigator: Carla H van Gils, PhD UMC Utrecht
Principal Investigator: Petra HM Peeters, MD PhD UMC Utrecht
Principal Investigator: Willem P Mali, MD PhD UMC Utrecht
  More Information

Additional Information:
No publications provided

Responsible Party: C.H. van Gils, Associate Professor of Clinical Epidemiology, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01315015     History of Changes
Other Study ID Numbers: UMCU DENSE, ZONMW-200320002-UMCU, Pink Ribbon-10074, BSP-DENSE, DCS-UU-2009-4348, DCS-UU-2014-6859, UMCU DENSE, <none>
Study First Received: March 14, 2011
Last Updated: August 2, 2014
Health Authority: The Netherlands: Ministry of Health, Welfare and Sports

Keywords provided by 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

ClinicalTrials.gov processed this record on August 21, 2014