Contrast-Enhanced Mammography (CEM)

Contrast-enhanced mammography (CEM), also known as contrast-enhanced spectral mammography (CESM) or contrast-enhanced digital mammography (CEDM), is an imaging technique that uses iodinated intravenous (IV) contrast in combination with a standard digital mammogram. Some cancers that are not visible on standard mammograms or tomosynthesis can be seen with contrast enhancement. The iodinated contrast agents used are identical to the contrast agents used for CT scans, but different from the gadolinium-based contrast agents used in MRI. CEM can be used to assess the extent of cancer in women with newly diagnosed breast cancer and to monitor response to neoadjuvant chemotherapy prior to surgery. CEM can be used to evaluate breast symptoms or abnormalities seen on mammograms. In women recommended for screening MRI, CEM can be performed as an alternative test. There are ongoing studies using CEM to screen women with dense breasts. Screening with CEM is currently considered an “off-label use” by the United States Food and Drug Administration.

Positioning and compression of the breast are the same as for a standard digital mammogram. Immediately before the CEM, an IV is placed into an arm vein for injection of a contrast agent. When the contrast is injected, the patient may momentarily feel warm all over, experience a need to urinate, and sense a metallic taste in her mouth. Imaging starts about two minutes after the contrast injection.

For CEM, for each breast, two mammographic exposures are obtained in each view: one using low-energy x-rays that mimics a standard mammogram, and one using higher energy x-rays that are absorbed by the iodine in the contrast agent. Low-energy and high-energy images are combined, typically as a weighted subtraction, to create an “iodine-only” image. Cancers typically have more vessels and leaky vessels relative to normal tissue and therefore more contrast agent. Areas where there is more of the contrast agent appear white on the “iodine-only” image. Normal breast tissue (dense and non-dense) and benign (noncancerous) lesions will usually appear dark on CEM. For this reason, most cancers are easier to see on the “iodine-only” images than on a standard mammogram or tomosynthesis. The radiologist will review the “iodine-only” images together with the low-energy images [1].

CEM has a higher cancer detection rate compared to standard mammography [1-3] and to the combination of mammography and breast ultrasound [4]. In a study of 904 women at elevated risk for breast cancer, 77% of whom had dense breasts, cancer detection rate for CEM was 15.5/1000 with 2 interval cancers [3]. Cancer detection rate of the low-energy images alone, which have an appearance and accuracy similar to standard digital mammograms, was 8.8/1000 [3].

Compared to MRI, CEM shows the same or nearly the same cancer detection rates [2, 5, 6] and can be performed at a lower cost than MRI. CEM can be added to standard digital mammography or tomosynthesis equipment, allowing it to be used in more radiology practices than MRI and increasing access for patients [7]. CEM is a relatively short examination, lasting about 10 minutes, comparable to an abbreviated/fast MRI and much less than the 30-40 minutes required for a standard breast MRI. CEM is generally better tolerated than MRI and poses no issue in patients with claustrophobia or metallic implants [8, 9].

The radiation dose of CEM is well within the range of other types of mammographic exams commonly performed [including standard 2D mammography, 3D mammography/tomosynthesis with synthetic 2D, or combined 2D and 3D mammography] and within the regulated MQSA dose [10].

Findings detected on CEM may be seen with ultrasound or in retrospect on 2D mammography or tomosynthesis.  They can then be targeted for biopsy using these imaging methods, if needed.  When a suspicious CEM finding cannot be seen on these other imaging exams, direct CEM-guided biopsy is appropriate, but this is not available yet at all centers. MRI-guided biopsy may be needed where CEM-guided biopsy is not available. It is important to discuss this possibility with the patient in advance of the CEM examination to assure that the patient can undergo an MRI if needed.

CEM should not be used to avoid biopsy of suspicious calcifications. Some cancers may be visible only as calcifications on the low-energy images and not show contrast enhancement on the “iodine-only” images.

Lastly, iodinated contrast agents carry some risks. Women with poor kidney function or a history of prior iodinated contrast reaction should avoid it. In women over age 60 or with a history of diabetes, hypertension, or family history of kidney disease (such as polycystic kidney disease), a drop of blood obtained when the IV line is started will typically be used to check kidney function prior to administering contrast. Mild allergic reactions, such as hives, occur in about 1% of patients within a few minutes of contrast administration. Severe allergic reactions resulting in anaphylaxis and possibly death are rare. The risk of death from a contrast reaction is estimated to be about 1 in 200,000, but, with staff trained in contrast reactions, this should be an extremely rare occurrence [11].