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

Conditions

Breast Cancer

Keywords

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

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).

van Grinsven SEL, Mann RM, Monninkhof EM, Duvivier K, de Jong MDF, de Koekkoek-Doll PK, Loo CE, Pijnappel RM, van der Sluijs R, Veltman J, van Gils CH, Veldhuis WB, DENSE Trial Study Group.

2025-05-012 citations

10.1148/radiol.241233

Deep Learning for Automated Triaging of 4581 Breast MRI Examinations from the DENSE Trial

Erik Verburg, Carla H. van Gils, Bas H. M. van der Velden, Marije F. Bakker, Ruud M. Pijnappel et al. (7 authors)

Radiology2021-10-0573 citations

10.1148/radiol.2021203960

Reducing False-Positive Screening MRI Rate in Women with Extremely Dense Breasts Using Prediction Models Based on Data from the DENSE Trial

Bianca M. den Dekker, Marije F. Bakker, Stéphanie V. de Lange, Wouter B. Veldhuis, P. J. van Diest et al. (47 authors)

Radiology2021-08-1723 citations

10.1148/radiol.2021210325

Supplemental Breast MRI for Women with Extremely Dense Breasts: Results of the Second Screening Round of the DENSE Trial

Stefanie G. A. Veenhuizen, Stéphanie V. de Lange, Marije F. Bakker, Ruud M. Pijnappel, Ritse M. Mann et al. (55 authors)

Radiology2021-03-16167 citations

10.1148/radiol.2021203633

Supplemental MRI Screening for Women with Extremely Dense Breast Tissue

Marije F. Bakker, Stéphanie V. de Lange, Ruud M. Pijnappel, Ritse M. Mann, Petra H.M. Peeters et al. (20 authors)

New England Journal of Medicine2019-11-27650 citations

10.1056/nejmoa1903986

Reasons for (non)participation in supplemental population-based MRI breast screening for women with extremely dense breasts.

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.

2018-06-1823 citations

10.1016/j.crad.2018.04.002

Interventions

OTHERContrast 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SCREENING

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

50 Years to 75 Years

Healthy volunteers

No

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)

Design outcomes

Primary

Measure	Time frame	Description
The number of interval cancers will be compared between the MRI group and the control group	8 years (with an interim analysis every two years; time period between two screening rounds)	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

Measure	Time frame	Description
Tumor size, stage and grade distributions, including their histological and molecular subtypes, diagnosed in both study groups will be compared	8 years (with an interim analysis every two years; time period between two screening rounds)	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	6 years (with an interim analysis every two years; time period between two screening rounds)	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	6 years (with an interim analysis every two years; time period between two screening rounds)	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 MRI screen-detected tumors will be determined	6 years (with an interim analysis every two years; time period between two screening rounds)	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	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 cost-effectiveness of MRI will be estimated using the MISCAN computer simulation program	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	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 number of biopsies per positive MRI will be determined	6 years (with an interim analysis every two years; time period between two screening rounds)	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.

Countries

Netherlands

Outcome results

None listed