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

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

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

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

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.

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).

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

The additional MRI will take place biennially after the regular screening mammogram for a study period of 6 years.

No further follow-up until next scheduled screening examination two years later (according to the current Dutch guideline).

Gadolinium contrast is administered as a bolus with a standard dose of 0.1 mL/kg followed by a saline flush of 30 mL.

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 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

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 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

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 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

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 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

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.

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)

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