For women with extremely dense breasts, screening with MRI alone every 4 years is cost-effective and delivers the greatest benefit, the first study of its kind indicates.
Alternatively, if a woman worries that the 4-year screening interval is too long, screening mammography may be offered every 2 years, with MRI screening offered for the second 2-year interval, according to the findings. This strategy would still require the patient to undergo MRI breast cancer screening every 4 years.
“MRI is more effective not only for selected patients. It is actually more effective than mammography for all women,” editorialist Christiane Kuhl, MD, PhD, University of Aachen, Aachen, Germany, told Medscape Medical News in an interview.
“But the superior diagnostic accuracy of MRI is more often needed for women who are at higher risk for breast cancer, and therefore the cost-effectiveness is easier to achieve in women who are at higher risk,” she added.
The study was published online September 29 in the Journal of the National Cancer Institute.
DENSE Trial
The simulation model used for the study was based on results from the Dense Tissue and Early Breast Neoplasm Screening (DENSE) trial, which showed that additional MRI screening for women with extremely dense breast tissue led to significantly fewer interval cancers in comparison with mammography alone (P < .001). In the DENSE trial, MRI participants underwent mammography plus MRI at 2-year intervals; the control group underwent mammography alone at 2-year intervals.
In the current study, “screening strategies varied in the number of MRIs and mammograms offered to women ages 50–75 years,” explains Amarens Geuzinge, MSc, University Medical Center, Rotterdam, the Netherlands, and colleagues, “and incremental cost-effectiveness ratios (ICERs) were calculated…with a willingness-to-pay threshold of €22,000 (>$25,000 US),” the investigators add.
Analyses indicated that screening every 2 years with mammography alone cost the least of all strategies that were evaluated, but it also resulted in the lowest number of quality-adjusted life years (QALYs) — in other words, it delivered the least amount of benefit for patients, co-author Eveline Heijnsdijk, PhD, University Medical Center, Rotterdam, Rotterdam, the Netherlands explained to Medscape Medical News.
Offering an additional MRI every 2 years resulted in the highest costs but not the highest number of QALYs and was inferior to the other screening strategies analyzed, she added. Alternating mammography with MRI breast cancer screening, each conducted every 2 years, came close to providing the same benefits to patients as the every-4-year MRI screening strategy, Heijnskijk noted.
However, when the authors applied the National Institute for Health and Care Excellence (NICE) threshold, MRI screening every 4 years yielded the highest acceptable incremental cost-effectiveness ratio (ICER), at €15,620 per QALYs, whereas screening every 3 years with MRI alone yielded an ICER of €37,181 per QALY.
If decision-makers are willing to pay more than €22,000 per QALY gained, “MRI every 2 or 3 years can also become cost-effective,” the authors add.
Asked how acceptable MRI screening might be if performed only once every 4 years, Heijnsdijk noted that in another of their studies, most of the women who had undergone MRI screening for breast cancer said that they would do so again. “MRI is not a pleasant test, but mammography is also not a pleasant test,” she said.
“So many women prefer MRI above mammography, especially because the detection rate with MRI is better than mammography,” she noted. Heijnsdijk also saod that the percentage of women with extremely dense breasts who would be candidates for MRI screening is small — no more than 10% of women.
At a unit cost of slightly under €300 for MRI screening — compared to about €100 for screening mammography in the Netherlands — the cost of offering 10% of women MRI instead of mammography might increase, but any additional screening costs could be offset by reductions in the need to treat late-stage breast cancer more aggressively.
“Interval” Cancers
Commenting further on the study, Kuhl pointed out that from 25% to 45% of cancers that occur in women who have undergone screening mammography are diagnosed as “interval” cancers, even among women who participate in the best mammography programs. “For a long time, people argued that these interval cancers developed only after the last respective mammogram, but that’s not true at all, because we know that with MRI screening, we can reduce the interval cancer rate down to zero,” Kuhl emphasized.
This is partially explained by the fact that mammography is “particularly blind” when it comes to detecting rapidly growing tumors. “The fact is that mammography has a modality-inherent tendency to preferentially detect slow-growing cancers, whereas rapidly growing tumors are indistinguishable from ubiquitous benign changes like cysts. [This] is why women who undergo screening mammography are frequently not diagnosed with the cancers that we really need to find,” she said.
Although there is ample talk about overdiagnosis when it comes to screening mammography, the overwhelmingly important problem is underdiagnosis. Even in exemplary mammography screening programs, at least 20% of tumors that are diagnosed on mammography have already advanced to a stage that is too late, Kuhl noted.
This means that at least half of women do not benefit from screening mammography nearly to the extent that they — and their healthcare practitioners — believe they should, she added. Kuhl underscored that this does not mean that clinicians should abandon screening mammography.
What it does mean is that physicians need to abandon the one-size-fits-all approach to screening mammography and start stratifying women on the basis of their individual risk of developing breast cancer by taking a family or personal history. Most women do undergo screening mammography at least once, Kuhl pointed out. From that mammogram, physicians can use information on breast density and breast architecture to better determine individual risk.
“We have good ideas about how to achieve risk stratification, but we’re not using them, because as long as mammography is the answer for everybody, there isn’t much motivation to dig deeper into the issue of how to determine risk,” Kuhl said.
“But we have to ensure the early diagnosis of aggressive cancers, and it’s exactly MRI that can do this, and we should start with women with very dense breasts because they are doubly underserved by mammography,” she said.
The study was supported by the University Medical Center Utrecht, Bayer HealthCare Medical Care, Matakina, and others. Geuzinge, Heijnsdijk, and Kuhl have disclosed no relevant financial relationships.
J Natl Cancer Inst. Published online September 29, 2021. Full text
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