Additional MRI screening for women with extremely dense breast tissue

https://www.nejm.org/doi/full/10.1056/NEJMoa1903986
Bakker, M. F.; de Lange, S. V.; Pijnappel, R. M.; Mann, R. M.; Peeters, P. H. M. and all, Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381(22):2091–2102 , DOI: 10.1056/NEJMoa1903986

Synthesis Cécile Bour November 28, 2019

Background

Extremely dense breast tissue is believed to be a risk factor for breast cancer, a factor that is especially limiting for cancer detection by mammography.

The aim is to test whether the use of MRI would reduce the occurrence of interval cancers, i.e. cancers appearing between two mammograms, the previous mammogram having been considered normal.

Method

This is a randomized controlled trial (study subjects randomly assigned to either group), multicentre (conducted in two or more centers with the same protocol and a coordinator responsible for processing all data and analyzing the results).

It is carried out by van Gils and his colleagues in the “DENSE” trial group.

The researchers divided 40,373 women between 50 and 75 years of age with extremely dense breast tissue and negative screening mammogram results, into two groups: either the “additional MRI” group or the “screening mammogram only” group; specifically 8,061 women in the “MRI-invitation” group and 32,312 women in the “mammogram-only” group.

A control mammogram was then performed after two years for both groups to compare the results in terms of the number of cancers found.

The main finding was the difference between the groups in the incidence of interval cancers over a two-year screening period.

The researchers stated that “Such patients 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. In the United States, a federal law directs breast-density reporting,but supplemental screening is not recommended in American guidelines. “

Although complementary imaging increases the rate of cancer detection in women with dense breasts, the question that remains is whether it improves health outcomes. Read about it: https://jamanetwork.com/journals/jama/article-abstract/2733521

Conclusion of the study

Additional MRI screening appears to be associated with fewer interval cancers compared to mammography alone in women with extremely dense breast tissue and normal mammography results. It appears that for dense breasts, the risk of interval cancers is reduced by half in women with negative mammograms and MRI screening.

Specifically, the researchers found that the interval cancer rate was 2.5 per 1,000 screenings in 4,783 women in the MRI-invitation group compared to 5 per 1,324 women in the mammography-only group.

Overall, 59% of women in the MRI group really attended this additional screening. Of the 20 interval cancers diagnosed in the group that was invited for MRI, 4 were diagnosed for women receiving MRI, and 16 were diagnosed for those who did not receive MRI.

Limitations of the study

  • False positives : Supplemental MRI scans were associated with a cancer detection rate of 16.5 per 1,000 screens and resulted in a false positive rate of 8.0% (79.8 per 1,000 screens). Among women who had a breast biopsy based on an MRI indication, 26.3% had breast cancer and 73.7% did not.
  • Sample not large enough.  To examine the effect of MRI screening on breast cancer specific mortality or overall mortality, the study would require a larger sample size and a longer observation period.

The lower rate of interval cancers observed in MRI participants may have an effect on mortality, but it would also be necessary to see a reduction in the number of advanced cancers in order to demonstrate a benefit on mortality reduction, which has not yet been demonstrated for mammography screening alone.

Reservations expressed 

In an accompanying editorial, Dan L. Longo, Associate Editor of the New England Journal of Medicine, and Professor. of Medicine at Harvard Medical School, (Boston), praised the high quality data from this unprecedented randomized trial: « It appears to show that among women with dense breasts, the risk of interval cancers is halved by following a negative mammogram with MRI screening ».

But the problem of over-diagnosis and the usefulness of additional screening in asymptomatic women, in whom lesions will be detected and be treated, without any evidence of survival or reduction in mortality, continues to be raised.

Dan Longo writes :

« But is a reduction in interval cancers an appropriate surrogate for improved overall survival? It appears that most of the cancers that were detected on supplemental MRI screening were found at an early stage. Ductal carcinoma in situ was 10 times more frequent among patients undergoing MRI, and these diagnoses were likely to lead to treatments. What remains unclear is whether the tumors would never otherwise have been detected or threatened the patient’s survival. »

« 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. 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. »

« So the dilemma remains. Women with dense breasts and a negative mammogram who undergo MRI have a very low risk of having breast cancer (16.5 per 1000 screenings in this trial) and an increased risk of a false positive scan. The findings of this trial are likely to reinforce the idea that MRI screening is important in women with dense breast tissue. But will we be putting these women at increased risk of procedures without contributing to their eventual survival? »

In addition, another study :

The concern about additional MRI screening is addressed in another controlled study of MRI screening for contralateral breast cancer patients in the United States. (Wang SY, Long JB, Killelea BK, et al. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurrence among older women with breast cancer. J Clin Oncol 2016;34:321-8.)

Although the incidence of invasive breast cancer in the contralateral breast after the screening period was lower with MRI screening than without screening, the overall incidence of breast cancer in the MRI group was twice as high as in the no MRI group, with no change in the incidence of advanced cancer throughout the five-year follow-up period. However, it is the incidence of advanced breast cancer that tells us whether or not screening is effective.

The researchers concluded :

“An increased synchronous contralateral breast cancer detection rate, attributable to MRI, was not offset by a decrease of subsequent contralateral breast cancer occurrence among older women with early-stage breast cancer, suggesting that preoperative MRI in women with breast cancer may lead to overdiagnosis.”

References

Bakker, M. F.; de Lange, S. V.; Pijnappel, R. M.; Mann, R. M.; Peeters, P. H. M. and all, Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381(22):2091–2102 , DOI: 10.1056/NEJMoa1903986

Longo, D.L, Detecting Breast Cancer in Women with Dense Breasts-Editorial, N Engl J Med 2019; 381:2169-2170 DOI: 10.1056/NEJMe1912943

Wang SY, Long JB, Killelea BK, et al. Preoperative breast magnetic resonance imaging and contralateral breast cancer occurence among older women with breast cancer. J Clin Oncol 2016;34:321-8.


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