For decades, X-ray-based mammography has been regarded as the gold-standard imaging modality for breast cancer screening. Since 2011, when the U.S. Food and Drug Administration approved contrast-enhanced mammography (CEM) as a clinical adjunct to mammography, CEM has emerged as a diagnostic tool that adds functional information with which clinicians may identify more quickly whether an abnormality in breast tissue is likely cancerous.
“Mammography and tomosynthesis are the standard of care for breast cancer screening, showing morphological information vital for detecting any changes in the breast,” said Abby Weldon, senior director of women’s health for Siemens Healthineers North America of Malvern, Pennsylvania. “Adding contrast to mammography can provide functional information like blood flow and oxygenation. This can provide a quick diagnostic advantage by visualizing atypical physiological processes.”
In addition to delivering diagnostic information faster and with a high degree of confidence, another principal benefit of CEM is as an alternative to magnetic resonance imaging (MRI), a diagnostic modality typically offered to women with dense breast tissue, or who might rely upon a scanner with higher-sensitivity capabilities. As Weldon points out, however, breast MRI is not as ubiquitous as mammography; neither is MRI purpose-built for breast imaging, as mammography machines are. And for women who can’t undergo an MRI for any number of reasons – an implanted medical device; an allergy to the gadolinium contrast agent upon which breast imaging with contrast relies; an inability to lie prone for the study – contrast-enhanced mammography can be a cost-effective alternative that delivers functional information earlier in the diagnostic process. Most importantly, Weldon said, CEM can help provide more women access to this functional technique and possibly help avoid unnecessary biopsies.
“Injection of contrast only needs to be done one to two minutes before the mammogram, and it’s a lot quicker than an actual MRI would be,” she said. “CEM functionality can be added to a normal mammography unit — which doesn’t have to be used just for contrast-enhanced mammography — and clinicians also can perform screening and biopsies on the same unit.”
In addition to the relatively rapid nature of a contrast-enhanced mammogram – the contrast agent decays within 10 minutes, and image acquisition typically only takes six to eight minutes – CEM costs about a quarter of what a breast MRI does. In a webinar prepared for Siemens Healthineers, Dr. Noel Bergquist, an assistant professor at the University of Tennessee at Knoxville Breast Center, said that women in her care have opted for CEM owing to its lesser expense and greater accessibility.
“A lot of my patients that are reluctant to pay for an MRI are happy to pay for this,” she said. “We’ve had no difficulties with insurance companies covering this modality.”
Additionally, Bergquist pointed out the high negative predictive value (NPV) of CEM: at 94 to 100 percent, the modality is effective at not returning false-negative results, and patients can be confident in the results of their study.
However, CEM isn’t without its drawbacks, among which Bergquist enumerated adverse reactions to the contrast agent, the potential for false-positive study results, and the possibly limited sensitivity of CEM given its ability to enhance images of normally functioning breast tissue, also known as background enhancement. Neither is CEM recommended for pregnant or breastfeeding women, those who are too young for a mammogram, women in renal failure, and, often, women with breast implants.
“Sometimes you are going to have to go to MRI, or you will have to biopsy based on landmarks,” Bergquist said. “But we have had great success at our center, and these challenges are minimal at most.”
Bergquist described finding the most effective uses of CEM in annual screenings of high-risk patients, for complicated cases, as a tertiary modality, and as an MRI alternative after neoadjuvant cancer treatment therapies already have been administered. It’s also useful in helping to determine the extent of disease in pre-surgical approaches to cancer treatment, as well as in cases of contralateral disease, in which breast masses are identified six months after detection of breast cancer in the opposite breast.
Siemens Healthineers’ chief platform for delivering CEM is the MAMMOMAT Revelation, which can be used to perform 3D mammography as well as titanium contrast-enhanced mammography, or TICEM, whereby a titanium filter helps alleviate the heat associated with dual-energy imaging. The Revelation also includes a feature that calculates the patient’s breast density after the first image is captured, which Weldon described as useful in assessing whether supplementary imaging is necessary.
“Any tools we can offer as vendors just to aid the facilities in helping inform women of their breast density are great,” she said, “but in the end, the only FDA-approved method for breast density assessment, or cancer diagnosis, is the radiologist’s assessment.”
Weldon said the install base for CEM is “totally mixed” across a variety of settings, from university to community hospitals. Currently, it’s less prevalently found at ambulatory clinics, but Weldon believes there’s opportunity for growth of the modality outside of hospital environments: in imaging centers, outpatient facilities, breast cancer centers and women’s health clinics.
“We do expect the utilization of CEM to grow,” Weldon said. “We’ve used MRI to identify breast cancer in a diagnostic setting or possibly for very high-risk women in a screening setting. However, MRI is not available everywhere due to a variety of reasons, including budget and space requirements. Although MRI is an extremely sensitive modality, CEM is expected to be a great alternative – especially for intermediate risk patients.”
Weldon also believes that the presence of a variety of medical imaging modalities reinforces clinical efforts to deliver personalized medicine for women with different types of breast health challenges, the better to tailor treatment appropriate for their distinct needs.
“Largely, we’re following the guidance of having a mammogram at the age of 40,” she said. “Care providers have urged for a more personalized approach, and for women to start to understand their potential risk earlier; to advocate for a modality that’s more in line with what their risk profile is. I think contrast-enhanced mammography offers a useful option to help enable risk-based screening.”
Scott Pohlman, director of outcomes research for Hologic Inc. of Marlborough, Massachusetts, also points out that contrast-enhanced breast imaging, whether mammography or MRI, can offer potential benefits “at various steps along the continuum of care.”
“At this time, exactly which women benefit from supplemental screening – and which type of supplemental screening is most appropriate – is not standardized, and depends on a variety of factors like a facility’s resources, a woman’s breast density, and insurance coverage, or if the patient has any health conditions that might eliminate certain modalities as an option,” Pohlman said.
“No patient is the same, and we need to tailor the breast cancer journey to fit each individual’s needs,” he said.
Despite the lack of consensus on the differences in sensitivity between CEM and MRI, Pohlman also pointed out that research into the use of both modalities indicates that each provides a higher sensitivity of image capture than mammography alone, as well as the capability of detecting breast lesions with a high degree of sensitivity.
“In a general sense, both CEM and contrast MRI depict the same fundamental physiological process – the accumulation of vascular contrast agent caused by the formation of new blood vessels (angiogenesis), which is associated with tumor growth,” he said. “As a result, there is a physiological reason to believe that they should both be able to detect malignant lesions that are not well visualized by more traditional anatomic modalities, such as mammography and ultrasound. However, CEM and MRI differ enough, particularly because acquiring multiple MRI images provides dynamic information about the rate of contrast enhancement, that some difference in performance should be expected.”
Ultimately, Pohlman concluded that the best way to more precisely measure the comparative effectiveness of CEM and MRI will require additional, large-scale studies of their relative performance in specific patient populations, because those studies undertaken to date have been too widely varied or too limited in scope. However, he also noted that feedback on patient experiences with CEM versus breast MRI patients has emphasized “faster procedure time, greater comfort, no issues with claustrophobia, lower anxiety and lower noise level,” as per a 2015 study published in the Journal of Medical Imaging and Radiation Oncology. Beyond that, however, there’s plenty to be said for the straightforward fulfillment of annual breast cancer screenings for women aged 40 and older.
“Something the medical community does agree on is that early detection and improved survival rates all start with regular breast screening beginning at age 40,” Pohlman noted. “In my opinion, the most impactful overall measure is that all women should be screened on digital breast tomosynthesis (DBT) – also known as 3D mammography – systems as a first step of the screening process, if they have the opportunity.”
DBT provides specific advantages for women with dense breast tissue as compared with 2D mammography alone, Pohlman notes; because dense breast tissue can mask small cancers, as both present similarly on imaging studies, which can potentially delay confirmation of a cancer diagnosis. As nearly half of all women in the United States may have dense breast tissue, DBT systems can help identify lesions that might be embedded beneath dense tissue by examining the breast, layer by layer.
“What is exciting is that the FDA recently released new data that showed DBT gantries now account for 46 percent of U.S. mammography imaging systems, with experts anticipating that DBT will replace the vast majority of full-field digital mammography (FFDM) systems in the next decade,” Pohlman said.
“Around the world, DBT is becoming the standard for breast imaging,” he continued. “In December 2022, the European Council updated the Article 168 recommendations to encourage the use of DBT for all breast cancer screenings. Additionally, in 2021, the European Commission Initiative on Breast Cancer (ECIBC) recommended for the first time that women with dense breast tissue could benefit from the use of DBT. These recommendations are monumental, as it creates an opportunity for more women to access DBT during their screenings.”
Pohlman also remarked on the significance of breast density inform laws in the United States as having an outsized impact on breast cancer detection. He believes that the continued advancement of legislative reforms related to health care screenings can only further those advancements.
“At Hologic, we applaud the FDA for their recent updates to the Mammography Quality Standards Act (MQSA) that require patient notification of breast density,” Pohlman said. “Prior to this, only 38 states and the District of Columbia mandated that facilities notify patients of their breast density. In addition to making this mandatory across the United States, it also creates a national standard for communicating about breast density.”
“However, there is still significant progress that needs to be made to address health care laws around screenings,” he said. “While the Patient Protection and Affordable Care Act (ACA) requires most health insurers to cover annual mammograms with no out-of-pocket expenses for women ages 40 years or older, this may not extend to supplemental screenings. For women with dense breast tissue, their health care providers may recommend supplementing mammography with whole breast ultrasound, CEM or MRI if their screenings are inconclusive.
“This leaves women with dense breast tissue to face additional barriers to care even though research shows they are at greater risk of breast cancer,” Pohlman said. “While many individual states have passed legislation mandating coverage for supplemental screening, inconsistencies remain between the states when it comes to which specific populations and modalities are covered, and whether the patients may be responsible for out-of-pocket costs associated with supplemental screening.”
