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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Contrast enhanced breast MRI


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 8 years (with an interim analysis every two years; time period between two screening rounds) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Breast neoplasm, Magnetic Resonance Imaging, Breast density, Early detection of cancer, Cancer screening test, Secondary prevention