Clinical trial NCT01315015: Breast Cancer Screening With MRI in Women Aged 50-75 Years With Extremely Dense Breast Tissue: the DENSE Trial
Official title: Breast Cancer Screening With MRI in Women Aged 50-75 Years With Extremely Dense Breast Tissue: the DENSE Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: Breast cancer
Breast neoplasm
Magnetic Resonance Imaging
Breast density
Early detection of cancer
Cancer screening test
Secondary prevention
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Dutch Breast Cancer Screening Organisations
name: Dutch Reference Centre for Screening
name: National Institute for Public Health and the Environment (RIVM)
name: The Netherlands Cancer Institute
name: University Medical Center Nijmegen
name: Jeroen Bosch Ziekenhuis
name: Albert Schweitzer Hospital
name: Hospital Group Twente (ZGT)
name: Amsterdam UMC, location VUmc
name: Maastricht University Medical Center
name: ZonMw: The Netherlands Organisation for Health Research and Development
name: Dutch Cancer Society
name: Pink Ribbon Inc.
name: A Sister's Hope
name: Bayer
name: Stichting Kankerpreventie Midden-West
name: Volpara Solutions
First posted: 2011-03-15
Enrollment: 40373
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

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.

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 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)

Primary outcomes:
measure: The number of interval cancers will be compared between the MRI group and the control group
timeFrame: 8 years (with an interim analysis every two years; time period between two screening rounds)
Secondary outcomes:
measure: The number of MRI screen-detected tumors will be determined
timeFrame: 6 years (with an interim analysis every two years; time period between two screening rounds)
measure: Tumor size, stage and grade distributions, including their histological and molecular subtypes, diagnosed in both study groups will be compared
timeFrame: 8 years (with an interim analysis every two years; time period between two screening rounds)
measure: The referral rate in the MRI study group will be determined
timeFrame: 6 years (with an interim analysis every two years; time period between two screening rounds)
measure: The positive predictive value (and the amount of false-positive diagnoses) of MRI will be determined using the histological diagnosis as the reference test
timeFrame: 6 years (with an interim analysis every two years; time period between two screening rounds)
measure: The number of biopsies per positive MRI will be determined
timeFrame: 6 years (with an interim analysis every two years; time period between two screening rounds)
measure: The mortality rate in the MRI group will be compared with the control group using the MISCAN computer simulation program
timeFrame: 8 years
measure: The cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program
timeFrame: 8 years
measure: The impact of MRI screening on quality of life will be assessed using standardized and validated questionnaires
timeFrame: 8 years
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Almelo
country: Netherlands
facility: Hospital Group Twente (ZGT)
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Hospital
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Hengelo
country: Netherlands
facility: Hospital Group Twente (ZGT)
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Carla H van Gils, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht
name: Wouter B Veldhuis, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.