It’s well known that mammography is the first line of defense when it comes to diagnosing breast cancer, but there is mounting evidence that contrast-enhanced breast MR can be a highly valuable secondary screening option for high-risk patients. HealthCare Business News spoke to experts in order to figure out how MR fits into the breast cancer screening conversation, and what its role will be in the future.

“I don’t think women know that this is the Royals Royce of breast cancer screenings – it hasn’t percolated,” said Dr. Elizabeth Morris, chief of breast imaging services and Larry Norton Chair at Memorial Sloan Kettering Cancer Center. “Physicians don’t know about it, either…there’s definitely an underutilization of MR.” She cited a recent U.S. study that found only about one percent of women who qualified for secondary breast screening due to higher risk factors were getting the exam.

Another study, published in the March issue of Journal of General Internal Medicine, concluded that, “Comparatively little is known about the use of [breast] screening MR in community practice," and "Utilization of screening MR in a community setting is not consistent with current professional guidelines and the goal of delivery of high-value care."

“As an organization, we are eager, but disciplined, to learn from published studies more about who is most likely to benefit from breast MR screening,” said Susan Brown, MS, RN, senior director of Education and Patient Support at Susan G. Komen, a nonprofit breast cancer awareness organization. “Individuals, however, can consult with their providers, who most likely base recommendations on clinical practice guidelines but also on professional judgment and discussion with their patients.”

The American College of Radiology (ACR) and the Society for Breast Imaging (SBI) have both put forth new MR contrast guidelines for women at higher risk for developing breast cancer. In a joint announcement in April, the ACR and the SBI assigned "special status" to African-American women, as well as women who have risk factors putting them at higher risk of breast cancer. This includes: a calculated lifetime risk of 20 percent or more, those who have received mantle radiation therapy at a young age, women who have previously been diagnosed with breast cancer by age 50, and women with dense breast tissue.

“[Breast MR] is out best screening test available, and we think it needs to be extended to more patient populations so that more people can benefit from it," Morris said.

A personalized approach
While there have been some differing directives concerning what age women should commence mammography screenings, the existing body of evidence shows that mammography is an excellent first line of defense against breast cancer. According to the ACR, since mammography became widespread in the 1980s, the death rate from the disease among women has dropped 39 percent.

“Microcalcifications show up on mammography that doesn't show up on breast MR, and very often microcalcifications are the first sign of breast cancer," said Brown. "The other thing is that specialized radiologists are required to interpret breast MR. So going to a facility that has the equipment and the radiologists specially trained … is important.”

At Yale University School of medicine, the program has evolved into a regional high-risk breast cancer referral center using digital breast tomosynthesis (or 3D mammography), but they still rely on MR screening for high-risk patients, according to Dr. Madhavi Raghu, assistant professor of radiology and biomedical imaging.

“The patients that are getting MR in our practice are patients [whose] malignancies are difficult to see on tomosynthesis or … they have extremely dense breasts – especially younger patients,” she said. “MR is especially useful for patients who have a strong family history or carry mutations … or younger patients. But for us, we're able to find some of these lesions with tomo before the patient gets [referred] to MR.”

Until recently, MR breast cancer screening with contrast (gadolinium) was reserved for “super high-risk” patients, according to Morris. But with the rapid advancement in technology – including risk factor tests women can buy on their own – individual breast cancer assessment is becoming more personalized.

“As we have entered in this new era of precision medicine and personalized screening, we realize that not everyone's risk is the same," Morris said. "There is a whole stratification of risk that we’re missing. There are women at intermediate risk of 12 to 20 percent, that’s what the new [ACR and SBI] guidelines are recognizing.”

MR secondary breast screening ‘lights up’ cancer for patients
In addition to finding breast cancers sooner, breast MR can also expose the aggressive forms of the disease before the cancer metastasizes. In a 2017 study published in Radiology, a German research team made the case that MR breast screening is also valuable for screening women at average risk of the disease, echoing Morris’ assertion that the procedure should not be limited to high-risk patients.

“In our observational study [on nearly 4,000 women] we have shown that one can avoid interval cancers altogether if one uses MR screening,” said Dr. Christiane Kuhl, a radiologist at RWTH Aachen University and lead author of the study. “In other words, none of the women who had undergone MR every year, or even every two or three years, had breast cancers diagnosed between screening rounds. All cancer in the cohort were detected by MR way before they were clinically palpable.”

Breast MR screening is so effective because it capitalizes on the increased blood flow of cancer in comparison to the surrounding breast tissue, according to Dr. Priti A. Shah, assistant professor at VCU Health. The scan essentially “lights up” even very small tumors with the aid of the contrast agent gadolinium.

Shah cited the case of a patient with dense breasts who had a screening mammogram and MR at age 41. With a sister and mother both diagnosed with breast cancer, this patient was considered high-risk. A sub-centimeter mass found in an MR scan was noted in the left breast, which had not been visible on her mammogram. A follow-up biopsy identified the mass as a high-grade cancer. Shah said because the cancer was found early and still small, the patient has an excellent prognosis for treatment and survival.

When 49-year old Laurel Pointer, affiliate communications manager for Susan G. Komen, discovered she was at high-risk for breast cancer she took a similar approach.

"My mom, sister, aunt, and cousin are all breast cancer survivors,” said Pointer. “About the time my aunt had breast cancer reoccur for the fourth time, my mother called to let me know that she had genetic testing and had the CHEK2 mutation. I was screened, and I also carry the mutation."

With the CHEK2 mutation, Pointer carries a lifetime risk of developing the disease that is 27 percent higher than normal. Adding in other risk factors, such as having no children and being slightly overweight, multiplies the risk. After consulting with a breast surgeon/oncologist, she opted to have an MR breast screening once a year between her annual mammograms, with the first MR screening scheduled for October.

Access and affordability
The speed at which a given diagnostic test becomes standard depends on the relationship between clinical practice and insurance coverage. Currently, the availability and insurance coverage for MR breast screening, as is typical with new clinical standards, seems to be in a gray area.

“In an ideal world if we had endless amounts of money and MR machines, probably all of us should have MR screenings, [but] it is an expensive test currently, and it does use an injection. There is not capacity to scan every woman in the U.S., every year.” said Morris with Sloan Kettering. “So, we want to recommend it for people who are going to be having breast cancer at higher rates than the general population.”

If a patient has a 20 percent lifetime risk, insurance typically covers MR breast screening, according to Dr. Kelly Myers, assistant professor of radiology at Johns Hopkins Hospital. She is optimistic that new innovations will help increase access to the scans.

“Recently, there has been much excitement about investigating abbreviated breast MR, which is a shortened version of the standard breast MR,” said Myers. “Studies so far have been very promising, and if abbreviated breast MR is able to find nearly as many cancers as the standard protocol MR, but with much less time in the MR, this could make the exam more affordable, and in turn, accessible to more patients.”

Shortcomings and uncertainties with MR breast screening
There are a few points of reserve to consider with MR breast screening. Dr. Christoph Lee, staff radiologist, Seattle Cancer Care Alliance and associate professor of radiology at the University of Washington School of Medicine, said that no trials have looked at the mortality benefit from supplemental MR screenings. Lee also said that patients should be informed about the possibility of false positives, which can create significant anxiety and lead to unnecessary treatment.

Still, Lee believes that women should have the choice to receive MR breast screening if they are at high lifetime risk.

“We don’t have randomized control trials looking at mortality as an endpoint, and we're never going to," Sloan Kettering’s Morris said. "We have to use surrogate endpoints – size, grade, nodule positivity – to show there is a benefit to the screening.”

Morris also believes that concerns over false positives are a holdover from earlier attempts at the application, which led to some recommendations for biopsies on benign masses.

“These days it doesn’t have that many false positives. It has a high detection rate, and when you do a biopsy, there's a high rate of positivity,” she said. “The problem, I think, is historical … that it got a reputation. But that’s not the breast MR of today.”

Since breast MR requires the use of the contrast agent gadolinium, which in some cases can cause adverse reactions and has come under new scrutiny as researchers investigate retention of the dye in the brain, some patients may be reluctant to undergo the exam.

“Surely no test in medicine is perfect, nor without risk,” said VCU Health’s Shah. “But for an otherwise healthy patient without kidney failure, or allergies to the dye, especially high-risk patients, the benefits of early breast cancer detection through MR are thought to outweigh the risks.”

Ultimately everyone seems to agree that these shortcomings pale in comparison to the value breast MR can bring to patients who need it most.

“On a regular basis, we find mammography-occult breast cancers in women at high lifetime risk undergoing screening MR,” said Lee, “These women likely benefit from earlier cancer detection at lower stages, and thus less aggressive treatment.”

Lining up the right patients with the right imaging modality can mean the difference between life and death. “Over 40,000 women die from breast cancer each year, and breast MR has the potential to find the most cancers when they are small and are highly treatable,” said Johns Hopkins’ Myers.