Randomised Trial of Supplemental MRI Screening in Women with Extremely Dense Breast Tissue

The results from the DENSE study

The use of supplemental magnetic resonance imaging (MRI) screening in women with extremely dense breast tissue and normal results on mammography resulted in the diagnosis of significantly fewer interval cancers than mammography alone during a 2-year screening period. The DENSE Trial Study Group reported the results in the 28th November 2019 issue of The New England Journal of Medicine and presented earlier this year the findings at the Clinical Trials in Radiology session at the European Congress of Radiology 2019.

The authors wrote in the study background that women with extremely dense breast tissue have an increased risk of breast cancer, and their cancers are also less likely to be detected on mammography. They may benefit from a tailored breast-screening strategy, supplemented with more sensitive imaging methods.

The benefit of supplemental imaging is the subject of a worldwide debate. Although supplemental imaging increases the rate of cancer detection in women with dense breasts, the question remains whether it improves health outcomes. The first indication for a reduction in morbidity and mortality is a reduction in the incidence of interval cancers, since such a reduction may mean that cancers that would otherwise have become symptomatic would now be detected earlier.

The Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial is a randomised, controlled trial to study the effect of supplemental MRI on the incidence of interval cancers in women with extremely dense breast tissue.

In this multicentre, randomised, controlled trial performed in the Netherlands, the study team assigned 40,373 women between the ages of 50 and 75 years with extremely dense breast tissue and normal results on screening mammography to a group that was invited to undergo supplemental MRI or to a group that received mammography screening only. The groups were assigned in a 1:4 ratio, with 8,061 in the MRI-invitation group and 32,312 in the mammography-only group. The primary outcome was the between-group difference in the incidence of interval cancers during a 2-year screening period.

The interval-cancer rate was 2.5 per 1000 screenings in the MRI-invitation group and 5.0 per 1000 screenings in the mammography-only group, for a difference of 2.5 per 1000 screenings (95% confidence interval [CI], 1.0 to 3.7; p < 0.001). Of the women who were invited to undergo MRI, 59% accepted the invitation. Of the 20 interval cancers that were diagnosed in the MRI-invitation group, 4 were diagnosed in the women who actually underwent MRI (0.8 per 1000 screenings) and 16 in those who did not accept the invitation (4.9 per 1000 screenings). The MRI cancer-detection rate among the women who actually underwent MRI screening was 16.5 per 1000 screenings (95% CI, 13.3 to 20.5). The positive predictive value was 17.4% (95% CI, 14.2 to 21.2) for recall for additional testing and 26.3% (95% CI, 21.7 to 31.6) for biopsy. The false positive rate was 79.8 per 1000 screenings.

Among the women who underwent MRI, 0.1% had either an adverse event or a serious adverse event during or immediately after the screening.

The authors concluded that they found that supplemental screening with MRI in women with extremely dense breast tissue resulted in the diagnosis of significantly fewer interval cancers than the use of mammography alone. The data from incident screening rounds and longer follow-up are needed in combination with simulation studies to assess the effect on the rate of advanced cancers and, eventually, on mortality.

The study was supported by the University Medical Center Utrecht, the Netherlands Organization for Health Research and Development, the Dutch Cancer Society, the Dutch Pink Ribbon–A Sister’s Hope, Bayer Pharmaceuticals, and Stichting Kankerpreventie Midden-West. For research purposes, Volpara Health Technologies provided Volpara Imaging Software, version 1.5, for installation on servers in the screening units.

 

Reference

Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI Screening for Women with Extremely Dense Breast Tissue. N Engl J Med 2019; 381:2091-2102. DOI: 10.1056/NEJMoa1903986.