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

• 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.
  
  

• 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.
  
  

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).