OTHER BREAST IMAGING IN DEVELOPMENT: Contrast-Enhanced Mammography (CEM)

What is it? Contrast-enhanced mammography (CEM) is also known as contrast-enhanced spectral mammography (CESM) or contrast-enhanced digital mammography (CEDM). CEM uses a standard iodinated intravenous (IV) contrast agent, such as would be used for a typical CT scan, in combination with mammography. Some cancers that may not be visible on standard mammograms will show up because of contrast enhancement. Similar to a CT scan, the contrast is injected into an arm vein. CEM can be used for problem solving and to assess the extent of disease in women with newly diagnosed breast cancer. There are ongoing studies using CEM to screen women with dense breasts. Screening with CEM is considered an “off-label” use by the United States Food and Drug Administration.

How it works: Positioning is like a standard mammogram, with the breast compressed. Beginning about two minutes after contrast injection, two exposures are taken in each view: one at low energy that mimics a standard mammogram, and one at higher energy that is absorbed by iodine; subtraction is performed to create an “iodine-only” image which is reviewed together with the low-energy image [1]. Just as for breast MRI, which is also done with contrast, cancers typically take up more of the contrast agent than does the surrounding normal tissue. The contrast agent contains iodine, which absorbs x-rays, causing the cancer to show up white on the mammogram. Normal breast tissue (dense and non-dense) and benign (noncancerous) lesions will mostly appear dark on CEM, though some benign lesions and background tissue can show enhancement.

Benefits: In multiple studies, CEM equaled or nearly equaled MRI [2-4] in its ability to detect breast cancer and was superior to the combination of standard mammography and breast ultrasound [5]. In a study of 904 women at elevated risk for breast cancer, 77% of whom had dense breasts, cancer detection rate was 15.5/1000 with 2 interval cancers; cancer detection rate of the low-energy images alone was 8.8/1000 [6]. Compared to MRI, CEM uses much less expensive, specially adapted, mammography equipment so it can be performed at lower cost. CEM is also a shorter examination, lasting about 10 minutes, versus 30-40 minutes for a standard breast MRI (and comparable to an abbreviated/fast MRI).

Considerations: CEM requires that an IV be placed into the arm for injection of the contrast agent. There is a small increase in the amount of radiation, about 50% more than for a standard mammogram, but less than that from combined 2D and 3D mammography (tomosynthesis) [7]. There is currently no FDA approved direct method to biopsy abnormalities seen only as areas of enhancement on contrast-enhanced mammography (though it is available in some centers in Europe), but many abnormalities can be located and biopsied with ultrasound. If not seen on ultrasound, MRI may be necessary to guide biopsy. Iodinated contrast agents carry some risks. Women with poor kidney function or history of prior contrast reaction should avoid it. Mild allergic reactions, such as those resulting in hives, occur in about 1% of patients. Severe allergic reactions resulting in anaphylaxis and even death are rare, but can occur. The risk of death from a contrast reaction is estimated to be about 1 in 200,000.

Figure 21. Contrast-Enhanced Mammography. Top: digital mammogram with cancer (red arrows), Bottom: contrast-enhanced mammogram in same patient; cancer is more visible.

References Cited

1. Lewin JM, Isaacs PK, Vance V, Larke FJ. Dual-energy contrast-enhanced digital subtraction mammography: Feasibility. Radiology 2003; 229:261-268

2. Jochelson MS, Dershaw DD, Sung JS, et al. Bilateral contrast-enhanced dual-energy digital mammography: Feasibility and comparison with conventional digital mammography and MR imaging in women with known breast carcinoma. Radiology 2013; 266:743-751

3. Jochelson MS, Pinker K, Dershaw DD, et al. Comparison of screening CEDM and MRI for women at increased risk for breast cancer: A pilot study. Eur J Radiol 2017; 97:37-43

4. Lewin J. Comparison of contrast-enhanced mammography and contrast-enhanced breast MR imaging. Magn Reson Imaging Clin N Am 2018; 26:259-263

5. Sorin V, Yagil Y, Yosepovich A, et al. Contrast-enhanced spectral mammography in women with intermediate breast cancer risk and dense breasts. AJR Am J Roentgenol 2018; 211:W267-W274

6. Sung JS, Lebron L, Keating D, et al. Performance of dual-energy contrast-enhanced digital mammography for screening women at increased risk of breast cancer. Radiology 2019; 293:81-88

7. Phillips J, Steinkeler J, Talati K, et al. Workflow considerations for incorporation of contrast-enhanced spectral mammography into a breast imaging practice. J Am Coll Radiol 2018; 15:881-885