Sharper Contrast
By Kathy Hardy
Radiology Today
Vol. 20 No. 10 P. 10

Contrast-enhanced mammography has the potential to reduce breast biopsies.

One topic under debate in the discussion of when and how often to screen women for breast cancer is the potential “harm” caused by screening exams. Of particular concern is the number of false-positive findings and breast biopsies that are ultimately found to be noncancerous. This issue is the catalyst for an ongoing study at the University of Pittsburgh Medical Center, where researchers are looking to bring more specificity to the screening process with contrast-enhanced mammography, an application that uses iodine contrast agent in conjunction with mammography.

Contrast-enhanced mammography has been shown to improve the determination of malignancy probability and BI-RADS assessment when compared with conventional mammography alone. It can be a useful adjunct to diagnostic mammography and a potential problem-solving and staging tool. Study findings to date show the potential for contrast-enhanced mammography to help not only find potential cancers but also be more specific in those findings.

“As physicians, we want to cause no harm. Having to perform an ‘unnecessary’ breast biopsy to prove that a woman does not have breast cancer could be considered a ‘harm’ of our current practice,” says study lead author and radiologist Margarita Zuley, MD, FACR. “The focus historically in breast imaging has been to ‘find the cancers,’ but we need to raise the bar by focusing on optimizing both detection—sensitivity—and specificity. In other words, we need to improve accuracy.”

In her work, Zuley used knowledge gained from interpreting MRI with gadolinium contrast. Gadolinium goes where blood flows and highlights areas that could be potential cancers. MRI has much higher sensitivity than mammography, and nonenhancing areas on MRI are highly unlikely to be breast cancer. Using this general concept, Zuley realized that contrast-enhanced mammography, which uses iodine contrast instead of gadolinium, would likely be able to better differentiate cancerous from noncancerous findings better than mammography or ultrasound. Potentially, it could significantly reduce the number of biopsies of noncancerous breast lesions found during mammography screening.

Regarding whether contrast-enhanced mammography has the potential to reduce the number of unnecessary breast biopsies, Susan Harvey, MD, Hologic’s vice president of global medical affairs in the breast and skeletal health division, says there are currently no other breast imaging modalities being used consistently to decrease benign breast biopsies. Hologic refers to their version of contrast-enhanced mammography as contrast-enhanced digital mammography (CEDM).

“Certainly, CEDM is superior to standard mammography in that multiple studies have shown enhanced accuracy for detecting breast cancer, and this suggests that CEDM may play a larger role in decreasing benign biopsies as greater adoption occurs,” Harvey says.

Promising Results
The University of Pittsburgh study looked at the relatively high biopsy rate of BI-RADS 4A and 4B lesions, which have a low to moderate suspicion of malignancy. Study details reported that the anatomic characterization of lesions using nonenhanced mammography, digital breast tomosynthesis (DBT), and ultrasound are insufficient to significantly improve the positive predictive value of a biopsy. However, contrast-enhanced mammography presents the potential for a high negative predictive value for classifying indeterminate findings as benign in mammograms or on ultrasounds performed without contrast.

Researchers investigated whether CEDM used during diagnostic evaluation could increase biopsy positive predictive value for soft tissue density lesions by reducing benign biopsies while not impacting the biopsy rate of cancers. The study involved 57 women between the ages of 34 and 75, with 60 BI-RADS of 4A or 4B soft tissue lesions diagnosed with mammography, DBT, or ultrasound. The women underwent CEDM immediately before undergoing biopsy. Radiologists reviewed the diagnostic exams and provided three BI-RADS scores in the order that they would perform the exams in the clinic: first for digital mammography/DBT, then for digital mammography/DBT with ultrasound, and finally for digital mammography/DBT and ultrasound with CEDM. Prior to CEDM, 72% of BI-RADS ratings were greater than BI-RADS 4. However, after CEDM, 60 of these were reclassified as less than BI-RADS 3, for a 35% average biopsy recommendation reduction.

“We found that contrast-enhanced digital mammography has a higher accuracy than ultrasound or 2D or 3D mammography,” Zuley says. “The sensitivity was superior to mammography/DBT and specificity was superior to ultrasound, suggesting that contrast-enhanced digital mammography could be a better way to determine the need for biopsy.”

As outlined in a whitepaper written by radiologist John Lewin, MD, of The Women’s Imaging Center in Denver, and Maxine S. Jochelson, MD, director of radiology for the Breast and Imaging Center at Memorial Sloan Kettering Cancer Center in New York, patients undergoing contrast-enhanced mammography have much the same experience as those undergoing a standard mammogram. With contrast-enhanced mammography, however, an IV is inserted into the patient’s forearm for the administration of iodinated contrast agent. Iodine volume is similar to that administered for CT scans. In two to 2.5 minutes after injection of iodine, the patient is positioned for two standard mammography views of each breast; dual-energy image pairs are acquired in each projection. Images are produced using a “weighted logarithmic subtraction of the low-energy image from the high-energy image.” This technique increases the visibility of the iodine while reducing the visibility of background tissue. Images are then sent to PACS for interpretation by the radiologist.

In Zuley’s experience, the entire contrast-enhanced mammography process takes approximately 15 minutes. She uses Hologic’s I-View CEDM, which is added to the facility’s existing Hologic mammogram system. Images can be read while the patient waits, she says, so there’s no need for them to return to the office for results, eliminating the anxiety of not knowing their results.

“Contrast-enhanced digital mammography reduces exam time for the patient compared to breast MRI and also reduces interpretation time compared to breast MRI,” Harvey says.

Criteria for Use
Zuley says iodine has a known reaction rate, which could be of particular concern to radiologists working in free-standing imaging centers. “It’s important for the team to be able to handle reactions,” she says. Iodine can also be of concern in an older patient population, who may already be experiencing impaired renal function.

Another factor for smaller imaging centers to consider is the lack of a CPT code for clinical use of contrast-enhanced mammography. Lewin says that while it is used widely in other countries, use in the United States is primarily limited to academic centers, where there is funding for methods such as this.

“You want to do what’s best for the patient, but there’s no incentive to use CEDM if there’s no reimbursement,” he says. “What tends to happen is, in order for something like CEDM to become a more mainstream tool, equipment manufactures need to push for the codes. The increase of dense breast notification could also serve as a catalyst for the creation of a code to cover CEDM.”

Other imaging centers have found no problem being reimbursed for contrast-enhanced mammography. Lake Medical Imaging in Central Florida uses GE Healthcare’s SenoBright contrast-enhanced spectral mammography (CESM) at its facilities, for additional evaluation after a screening mammogram. The practice has been using the technology since 2014. At Lake Medical Imaging, they code the procedure as a diagnostic mammogram, a code that does not specify with or without contrast, says managing physician Catherine Keller, MD. The contrast cost is approximately $8 to $10, but Keller notes that the contrast cost is specific to Lake Medical Imaging’s purchasing contract.

“We do the best we can for the patient,” she says. “In Florida, we have the lowest Medicare reimbursement rate in the country, so, compared to breast MRI, SenoBright works for us. In Florida, SenoBright reimbursement is about $160. We have no problem with reimbursement, compared to many denials for breast MRI.”

Also in their whitepaper, Lewin and Jochelson address the need for better screening and supplemental imaging, particularly for women with dense breasts.

“The sensitivity of mammography for the detection of cancer in screening populations ranges from approximately 60% to more than 90%, depending on breast density, meaning that in the densest breasts, 4 of 10 cancers will not be detected by screening mammography prior to their becoming palpable,” the authors state. “Contrast-enhanced breast MRI has a much higher sensitivity.”

Jochelson says that in her setting at Memorial Sloan Kettering, most of her patients are already cancer survivors. With that, they use contrast-enhanced mammography “in a big way” for the regular screening these women need. “In women where you want better screening, contrast-enhanced digital mammography is a good option,” she says.

Keller agrees that contrast-enhanced mammography can play a valuable role in cancer detection for women with dense breasts and other risk factors. Keller’s protocol for women with dense breasts and/or family history of breast cancer is to perform contrast-enhanced mammography every other year, with DBT and automated breast ultrasound the alternate years. “We use as many tools as we have to see if something’s there,” she says.

A majority of Keller’s patient population is age 65 and older, with a variety of medical histories, which makes contrast-enhanced mammography a useful option. “CESM is good for women who have had BI-RADS findings during screening mammography,” she says. “It’s also good for women who already have scar tissue in their breasts from a previous lumpectomy. And it’s a good alternative for women who cannot undergo MRI or simply find MRI too uncomfortable to endure.”

Other Considerations
Keller says contrast-enhanced mammography results are similar to MRI but come with some added benefits that support her practice’s patient-centric approach. “The SenoBright is a fast, easy-to-use exam that gives us same-day results,” she says. “It’s a less expensive process than MRI and doesn’t have the limitations that MRI can have. There’s often more patient anxiety with MRI, especially if the patient has never had an MRI before. With CESM, the setting is the same as having a mammogram, and women are more accustomed to that experience.”

A vital point in the comparisons between MRI and contrast-enhanced mammography comes down to what radiologists can see. “In comparison to MRI, contrast-enhanced digital mammography has about the same sensitivity,” Lewin says. “MRI finds more cancers than mammography alone, while contrast mammography helps reduce false-positives. The key is sensitivity.”

Lewin adds that biopsy costs are another reason contrast-enhanced mammography may improve medical care. “A biopsy is a minimally invasive procedure that our patients don’t seem to mind,” he says. “However, the cost of a biopsy is about $1,000, while the cost of contrast-enhanced digital mammography is about $300 to $400.” He says that, with more studies underway, results could help create a greater priority to establish a CPT code for reimbursement of CEDM.

GE Healthcare’s chief marketing officer for women’s health, Annemijn Eschauzier, says CESM has the potential to reduce breast biopsies. “The negative predictive value of CESM is good,” she says. “If nothing lights up on the images, there’s no cancer. The results are similar to MRI but with better specificity. Contrast-enhanced spectral mammography is also a reduced-cost option to MRI. We hear users refer to CESM as a ‘better mammogram.’”

According to Eschauzier, it takes two minutes after the patient receives the IV iodine for images to be acquired, without the patient leaving the room. The entire process has a seven-minute turnaround time, she says.

Keller adds that she will also use contrast-enhanced mammography for patients who are new to the practice and do not have any prior mammograms available at any of the practice’s locations. “CESM gives us a good baseline to use going forward,” she says.

Jochelson says there is an increased focus on contrast and its potential benefits in breast cancer screening and diagnosis. There are the medical benefits to patients but also considerations of the patient experience.

“We’re still in the early days of this research, looking at a variety of small trials,” Zuley says. “There is the potential to use CEDM rather than MRI, with better specificity. There’s much discussion around screening changes when you develop technology like this.”

— Kathy Hardy is a freelance writer based in Phoenixville, Pennsylvania. She is a frequent contributor to Radiology Today.