November 27, 2019
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Supplemental MRI screening reduces interval cancer diagnosis rate among women with dense breasts

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Carla H. van Gils, PhD
Carla H. van Gils

Supplemental MRI screening appeared associated with significantly fewer interval cancer diagnoses compared with mammography alone among women with extremely dense breast tissue and normal results on mammography, according to results of the randomized DENSE trial published in The New England Journal of Medicine.

“Dense breasts are a risk factor for breast cancer, and dense tissue limits cancer detection by mammography. Supplemental imaging with MRI in these women has the potential to improve early detection,” Carla H. van Gils, PhD, professor in the department of epidemiology at Julius Center for Health Sciences and Primary Care of University Medical Center Utrecht in the Netherlands, told Healio. “This is the first time that this research question has been addressed in such a thorough way, and with supporting evidence as a result.”

The multicenter, randomized controlled trial by van Gils and colleagues included 40, 373 women with extremely dense breast tissue and normal results on screening mammography who either received an invitation to undergo supplemental MRI (n = 8,061; median age, 55 years) or underwent mammography screening alone (n = 32,312; median age, 54 years).

The between-group difference in incidence of interval cancers — cancers that are diagnosed between screening rounds when a tumor is so advanced that it causes symptoms or pain — during a 2-year screening period served as the study’s primary endpoint. Secondary endpoints included the recall rate for additional examination, cancer-detection rate on MRI, false-positive rate and positive predictive value.

Results of the intention-to-screen analysis showed an interval cancer rate of 2.5 per 1,000 screenings in the MRI-invitation group compared with five per 1,000 screenings in the mammography-alone group (difference, 2.5 per 1,000; 95% CI, 1-3.7).

Overall, 59% (n = 4,783) of women assigned to the MRI group underwent the supplemental screening.

Twenty interval cancers were diagnosed in the MRI-invitation group, of which four were diagnosed among women who accepted the invitation to undergo MRI (0.8 per 1,000 screenings) compared with 16 among those who did not (4.9 per 1,000 screenings).

The researchers estimated supplemental screening among a subgroup of women who would have accepted it had it been offered was associated with an interval cancer rate that was lower by 4.2 per 1,000 screenings (95% CI, 2-6.4) when compared with mammography alone (P < .001).

Among women who underwent MRI screening, researchers observed an MRI cancer-detection rate of 16.5 per 1,000 screenings (95% CI, 13.3-20.5). Moreover, the recall rate was 94.9 per 1,000 screenings (95% CI, 86.9-103.6). The positive predictive value for recall for additional testing was 17.4% (95% CI, 14.2-21.2) and 26.3% (95% CI, 21.7-31.6) for biopsy, with a false-positive rate of 79.8 per 1,000 screenings (95% CI, 72.4-87.9) and a specificity of 92%.

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Of the 300 women who underwent breast biopsy as a result of supplemental MRI screening, 64 were diagnosed with invasive breast cancer and 15 were diagnosed with ductal carcinoma in situ.

Adverse events during or immediately after MRI occurred among 0.1% of women who underwent MRI.

“There are still questions to be answered,” van Gils told Healio. “In an upcoming study, we are using the results in a mathematical model to estimate the impact on longer-term outcomes. With this, we can estimate the impact on breast cancer mortality and also the amount of overdiagnosis. It allows us to carefully weigh all the harms and benefits, including the costs and the higher number of false-positives.”

Researchers also are completing the second and third rounds of the DENSE study, van Gils said.

“It is important to see how many and what types of breast cancer we find,” she said. “It is also important to see what this does to the false-positive rate, as radiologists will have prior MRIs they can compare with. We will also use these outcomes of the incident rounds in the modeling to look for the optimal screening frequency for supplemental MRI.”

The ultimate test of the value of MRI screening among women with extremely dense breast tissue will be whether it extends survival — an answer we will not have for a very long time, Dan L. Longo, MD, hematologist at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, wrote in an accompanying editorial.

“In the meantime, we now have a trial showing that MRI screening can lead to a lower rate for 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,” Longo wrote. – by Jennifer Southall

For more information:

Carla H. van Gils, PhD, can be reached at the Julius Center for Health Sciences and Primary Care, Stratenum 6.131, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508 GA, the Netherlands; email: c.vangils@umcutrecht.nl.

Disclosures : The study was funded by Bayer Pharmaceuticals, the Dutch Cancer Society, Dutch Pink Ribbon — A Sister’s Hope, the Netherlands Organization for Health Research and Development, Stitchting Kankerpreventie Midden-West and University Medical Center Utrecht, with screening software provided by Volpara Health Technologies. van Gils reports no relevant financial disclosures. Please see the study for all authors’ relevant financial disclosures. Longo reports employment by The New England Journal of Medicine as deputy editor.