Mixed Results With Mammo Plus MRI Screening

Supplementing mammography with magnetic resonance imaging (MRI) for patients with dense breast tissue reduced the rate of interval cancers by half, but with a “concerning” rate of recall for additional imaging or interventions, Dutch investigators reported.

During the 2-year screening period, the rate of interval breast cancer was 2.5 per 1,000 mammographic screenings for women who underwent supplemental MRI and 5.0/1,000 in the patients who had mammography alone, said Carla van Gils, PhD, of the University Medical Center Utrecht, and colleagues. Four of 20 interval cancers in the MRI group occurred in women who accepted the invitation for supplemental imaging (0.8/1,000), and the remaining 16 interval cancers occurred in women who declined the invitation (4/1,000).

Supplemental MRI was associated with a cancer detection rate of 16.5/1,000, a false-positive rate of 79.8/1,000, and a recall rate of 94.9/1,000, the team reported in the New England Journal of Medicine (NEJM).

“The recall rate … is a concern for potential implementation of supplemental screening,” the researchers wrote. “Therefore, we are now evaluating methods for minimizing false-positive outcomes.”

“We 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,” van Gils and co-authors added. “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 provided high-quality data from a first-ever randomized comparison with mammography alone or with supplemental MRI, but the role of MRI in breast cancer screening remains unclear, NEJM deputy editor Dan L. Longo, MD, said in an accompanying editorial.

“The ultimate test of the value of MRI screening in women with extremely dense breast tissue will be whether its use improves survival — an answer that we will not have for a very long time,” Longo wrote. “In the meantime, we now have a trial showing that MRI screening can lead to a lower rate of interval cancers. The cost is that 74% of the biopsies that are subsequently performed will not lead to a cancer diagnosis, and we do not know whether the cancers that were detected needed to be found or treated.”

“The findings of this trial are likely to reinforce the idea that MRI screening is important in women with dense breast tissue,” he continued. “But will we be putting these women at increased risk of procedures without contributing to their eventual survival?”

Dense breast tissue increases a woman’s risk of breast cancers, and mammography is less likely to detect breast cancers that develop in dense tissue. The potential value of supplemental imaging remains a source of worldwide debate, van Gils and co-authors noted. In the U.S., federal law mandates reporting of breast density, but supplemental screening for women with dense breast tissue is not recommended in current clinical guidelines.

“Although supplemental imaging increases the rate of cancer detection in women with dense breasts, the question remains whether it improves health outcomes,” the authors said.

Study Details

In an effort to accumulate informative data on the issue, the investigators performed the DENSE trial, comparing breast cancer screening with mammography alone versus mammography plus supplemental MRI in women with dense breast tissue. Key inclusion criteria were age (50-75), extremely dense breast tissue (grade 4 by Volpara imaging software), and a negative screening mammogram.

The researchers randomized 40,373 patients 1:4 to receive an invitation for supplemental MRI or no further imaging beyond mammography. The primary outcome was the difference in the incidence of interval cancers during the 2-year screening round. The authors reported that 59% of patients randomized to supplemental MRI accepted the invitation.

The primary analysis showed a significant 2.5/1,000 reduction in the frequency of interval cancers in favor of the MRI group (95% CI 1.0-3.7, P<0.001).

The positive predictive value (PPV) for recall for additional testing in the MRI group was 17.4%, and the PPV for biopsy was 26.3%, meaning that 83% of recalls and 74% of biopsies yielded negative results. Among women who underwent MRI, 0.1% had an adverse event or serious adverse event during or immediately after screening.

The authors acknowledged that the trial lacked statistical power to evaluate the effect of MRI on breast cancer-specific or overall mortality, adding that the reduction in interval cancers in the MRI group suggested an effect on mortality. A reduction in advanced cancers would also be required to show a mortality benefit, which would require several years of follow-up.

“Thus, we are now using our results in a simulation study to evaluate the reduction in mortality and the extent of overdiagnosis, together with the effects on costs and quality of life,” the researchers stated.