Adding MRI to routine biennial mammography screening for women aged 40 years or older with extremely dense breasts and increased breast cancer risk showed promise for reducing breast cancer deaths in a modeling study.

Supplemental MRI imaging had similar harm-benefit ratios to biennial 3D mammography using digital breast tomosynthesis (DBT) in the simulations performed for the study. However, for supplemental MRI to be cost-effective, MRI costs and false positive biopsy rates must come down, according to the investigators.

The findings, by Anna N.A. Tosteson, ScD, of The Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and colleagues, were reported online in the Annals of Internal Medicine.

Gilbert Welch, MD, who was not involved with the study, cautioned against assuming that getting a breast MRI is linked to a reduced risk of dying from the disease.

The study provides “no new data regarding the effectiveness of breast MRI in averting breast cancer death,” he told Medscape Medical News.

“Instead, the article reports the output from three simulation models that estimate deaths averted based on the shift in tumor stage and size. These projections are derived from assumptions embedded in the models — not direct evidence that MRI screening prevents death,” explained Gilbert, of the Center for Surgery and Public Health at Brigham and Women’s Hospital in Boston.

Gilbert added that although it is challenging to “get inside the model’s ‘black box,’” he worries that “any additional detection is implicitly credited as producing a benefit.”

If so, the model risks equating more cancer detection with more deaths averted, he said.

Why MRI?

Breast density can reduce the sensitivity of screening mammography, and as of September 2024, an FDA mandate requires that patients who undergo mammography be notified if they have dense breasts.

“Those with dense breasts, who comprise an estimated 43% of the mammography screening population, are directed to discuss screening options with their health professionals,” the investigators noted.

But “[c]onsiderable uncertainty remains about the best screening approaches for women with dense breasts,” they added.

Underscoring that uncertainty, the 2024 US Preventive Services Task Force (USPSTF) guidelines stated there is insufficient evidence to recommend supplemental screening to otherwise average-risk women based on breast density alone.

Given the FDA mandate that requires patients who undergo mammography be notified if they have dense breasts, and the increasing interest in personalized risk-based screening, the investigators aimed at evaluating potential strategies for supplemental MRI screening.

Modeling Outcomes

The authors of the new study used evidence from the Breast Cancer Surveillance Consortium and the literature, along with models from the Cancer Intervention and Surveillance Modeling Network, to perform simulations of women aged 40 years or older with average-to-fourfold increased relative risk for breast cancer undergoing DBT with or without supplemental MRI. Simulations varied by age of screening initiation and screening intervals.

Across all starting ages and intervals, DBT averted 7.4-10.5 breast cancer deaths per 1000 average-risk women and 23.2-33.6 per 1000 with risk that was fourfold higher than average. Adding MRI screening for women with extremely dense breasts averted 0.1-0.8 additional breast cancer deaths per 1000 women across all relative risk levels.

Adding MRI also resulted in 22-186 additional false positive biopsy recommendations, the investigators reported. They noted that the rate of false biopsies per breast cancer death averted with biennial DBT plus MRI was similar among women with average risk and with two times higher-than-average risk.

For all risk groups, biennial DBT plus MRI starting at age 50 years was more effective, but less cost-effective, than DBT alone starting at age 45 years.

“Our analysis highlights the importance of considering both age group-specific breast cancer risk and density prevalence in identifying strategies where adding MRI to DBT has similar or better harm-benefit tradeoffs vs undergoing DBT screening alone,” the investigators wrote. “Our study provides needed modeling evidence to inform clinicians, women, and policymakers of the potential value of supplemental breast MRI based on density and risk.”

Supplemental Screening in Practice

The findings also underscore the need for clearer guidelines for the use of supplemental imaging in women with dense breasts, according to Elena B. Elkin, PhD, MPA, and Julia E. McGuinness, MD, MS, of Columbia University in New York City.

In an editorial, Elkin and McGuinness said the study by Tosteson and colleagues “reinforces the growing movement to tailor breast cancer screening by individual breast cancer risk” but pointed out that existing guidelines are conflicting and pose a barrier to the use of such personalized screening.

“Breast density notification should, ideally, empower women to have informed discussions with their clinicians about personalized breast cancer screening options, including the addition [MRI],” they noted. “Unfortunately, breast density notification laws preceded the scientific evidence necessary to support guidelines for supplemental imaging in women with dense breasts, which require careful balancing of potential benefits and harms of a more intensive screening approach.

“No fewer than six scientific and professional organizations in the United States have issued unique guidelines or position statements on screening mammography,” they added, citing a survey that found clinicians’ recommendations “varied sharply based on which guidelines the clinicians trusted most.”

In the DENSE trial published in 2019 in The New England Journal of Medicine, supplemental MRI in women with extremely dense breasts was associated with fewer interval cancers, but “only about 10% of women have extremely dense breasts, and the study findings may not be generalizable to the United States, where many women receive screening annually,” Elkin and McGuiness noted.

They also stressed the increased risk for false positive results, which can be associated with psychological distress and financial costs.

Findings from the DENSE trial contributed to the development of the USPSTF guidelines noting insufficient evidence for the use of supplemental MRI in average-risk women with dense breasts, they noted.

“Identifying the populations for whom supplemental breast MRI is most beneficial is necessary to fill this gap in clinical guidelines,” they stressed.

Furthermore, “Integration of breast cancer risk assessment into routine clinical practice will likely require a multipronged approach that aims to streamline risk assessment for both patients and their clinicians,” they said.

“Such approaches could include automation of risk assessment using information already captured in the electronic health record, clinical decision support tools to educate patients and clinicians about risk-based screening, and artificial intelligence models applied to mammograms that could enhance risk assessment through evaluation of features beyond density,” they suggested.

As reported recently by Medscape Medical News, a national move toward risk-based screening appears likely in the wake of other recent modeling studies and the WISDOM trial showing that risk-based screening was acceptable to women and noninferior to annual mammograms over 5 years.

Such a move could provide “an opportune catalyst for consensus building,” according to Elkin and McGuinness.

“Breast cancer risk assessment and screening continue to evolve toward finding the right test for the right person at the right time. Now, our guidelines must evolve to meet the needs of women and their clinicians,” they wrote.

Potential Harm of Overdiagnosis Missing From Study

One thing the investigators didn’t specifically address is the potential harm of overdiagnosis, “which is the central concern with breast MRI,” Welch said.

The DENSE trial showed that more than half of the MRI-detected cancers (5.4 of 9.8 cancers per 1000 screenings) grow so slowly that they are not apparent on a mammogram 2 years later.

“That finding raises the possibility that many MRI-detected cancers are indolent or may even regress, and would never become clinically evident — the definition of overdiagnosis,” Welch said.

He also pointed to Figure 1 in the new paper, which shows the mean screening benefits and harms with supplemental MRI vs no screening.

“[The data] contrasts how little MRI adds to the number of deaths averted and how much MRI adds to the number of unnecessary biopsies. That contrast deserves as much attention as the mode’s estimates of deaths averted,” he said.

The modeling study was funded through grants from the National Cancer Institute. Tosteson reported having no relevant disclosures. Welch reported receiving royalties from three books, including Should I Be Tested for Cancer?

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.