For breast imaging, contrast-enhanced mammography, which uses the anatomic imaging of a mammogram in addition to imaging neovascularity, can offer the overall screening capability of standard mammography and the sensitivity of magnetic resonance imaging (MRI) at a fraction of the cost of MRI, according to Maxine S. Jochelson, MD, Director of Radiology, Breast and Imaging Center at Memorial Sloan Kettering Cancer Center (MSKCC), New York. Dr. Jochelson explained why she is an advocate of this approach for breast screening during a lecture at the 2020 Miami Breast Cancer Symposium.1
Maxine S. Jochelson, MD
Pros and Cons of Screening Methods
Despite controversy about the utility of screening in general, mammography has been shown to reduce breast cancer mortality by about 30% in large randomized trials. It is an inexpensive tool and is widely available, but its sensitivity decreases in women with dense breasts.
To find the cancers missed by mammography, screening is often supplemented with ultrasound. Many studies have demonstrated that ultrasound does detect an additional 3.5 cancers per 1,000 women; however, in the large ACRIN 6666 trial, MRI was even more sensitive.2 Among 612 women who underwent MRI after three negative screenings with mammography plus ultrasound, 16 additional cancers were detected: 9 were not visible on mammography and/or ultrasound, even knowing where to look, and 8 were invasive. “That’s 56% of cancers seen only on MRI,” Dr. Jochelson said.
“Mammography plus ultrasound may be giving women with dense breasts a false sense of security. Every study of women at increased risk for breast cancer has shown that MRI finds at least 45% of cancers in that setting that are not found by mammography and ultrasound.”
“Mammography plus ultrasound may be giving women with dense breasts a false sense of security."— Maxine S. Jochelson, MD
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The sensitivity of MRI comes from the use of contrast to detect neovascularity, which makes cancer visible through enhancement of vessels, before it is obvious on mammography. Yearly MRI, which preferentially detects higher-risk cancer, greatly reduces the interval cancer rate, which is a surrogate for better outcomes.
“However, we have a problem,” Dr. Jochelson emphasized. “In this country, we have 25 million women with dense breasts and 3 million breast cancer survivors who require better screening as well. Despite the fact that MRI has very high sensitivity (approximately 97%), it is expensive (> $4,000), women don’t always like it, and it’s not always possible to get MRI to everyone who needs it.”
Abbreviated MRI: Benefits and Challenges
To offer better accessibility—and lower cost as well, perhaps—Christine Kuhl, MD, and colleagues in Germany developed abbreviated MRI.3 In contrast to conventional MRI, which typically involves 15 to 25 sequences taken over 30 minutes, abbreviated MRI takes 3 sequences in less than 10 minutes. “The whole abbreviated MRI protocol took just 28 seconds to read with exquisite sensitivity,” commented Dr. Jochelson. Many other investigators have been able to replicate these successful results in women at increased risk. The data demonstrate that, even in mutation carriers, the sensitivity is equal to and the specificity is better than conventional MRI.
Christine Kuhl, MD
The ACRIN/ECOG group led by Dr. Chris Comstock recently reported results of a prospective study of 1,516 women with dense breasts and no other risk factors to determine the utility of abbreviated MRI compared to tomosynthesis in a group of women with even fewer risk factors.4 Performed at both academic and private practices, abbreviated MRI was able to be done in less than 10 minutes in 97% of patients; detected all cancers except for one ductal carcinoma in situ; and achieved a cancer detection rate of 11.8/1,000 vs 4.8/1,000 for tomosynthesis. Abbreviated MRI detected 143% more cancers than tomosynthesis.
“Despite the success of this approach, the problem is that we may still not have the capacity to screen millions of women with MRI, even if they are shorter scans, because not every institution has multiple available MRI scanners like mine does,” she said.
“The data demonstrate that, even in mutation carriers, the sensitivity [of abbreviated MRI] is equal to and the specificity is better than conventional MRI.”— Maxine S. Jochelson, MD
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Contrast-Enhanced Mammography: ‘Available and Inexpensive’
Enter the newest approach: contrast-enhanced mammography, which was developed to mimic MRI’s capability of enhancing neovascularity to find and stage earlier cancers. Contrast-enhanced digital mammography uses a mammography machine with an upgrade that allows for dual-energy imaging. It uses the same iodinated contrast as for computed tomography [CT]) and is “available and inexpensive,” noted Dr. Jochelson.
The patient receives an injection of contrast and, after approximately 2.5 minutes, undergoes what she perceives as a standard mammogram, which obtains four views within 5 minutes. The exam yields a low-energy image (equivalent to a regular mammogram) and a high-energy one. The images are processed yielding a recombined or iodine image that shows enhancing lesions in the breast. In studies of this approach performed around the world, contrast-enhanced mammography has shown a sensitivity ranging from 93% to 100% in the diagnostic setting.
Dr. Jochelson and her team were the first to prospectively compare the use of contrast-enhanced digital mammography to MRI for screening in 307 women at increased risk for breast cancer. These women had been heavily prescreened with MRI.5 “So, the good news is those patients had a very small number of breast cancers,” stated Dr. Jochelson. “The bad news is the study did not produce good data on sensitivity, but, in fact, we were able to demonstrate that contrast-enhanced digital mammography can find cancers not seen on regular mammography in a fashion similar to MRI.” Three cancers (two invasive lobular cancers, one ductal carcinoma in situ) were detected during the first round of screening: MRI detected all three and contrast-enhanced digital mammography detected the two invasive cancers. None of the three cancers was seen on the low-energy mammograms, which are comparable to conventional mammography. At 1-year follow-up, two cancers were detected by screening imaging, neither of which were symptomatic cancers.
Contrast-Enhanced Mammography: Uses at Memorial Sloan Kettering Cancer Center
- To screen intermediate- or high-risk women
- To screen women with dense breasts
- To call back women from screening of abnormal mammograms
- To evaluate symptomatic patients
- To stage known cancers
- To follow-up after neoadjuvant chemotherapy
- To monitor patients after lumpectomy
- To improve biopsy selection site
Drs. Sung, Jochelson, and colleagues at MSKCC also conducted a retrospective study of baseline contrast-enhanced digital mammography in 904 women with dense breasts or other high-risk factors.6 They found that contrast enhancement detected 15.5 cancers per 1,000 women, which was the same detection rate they found with MRI, but at 10% of the cost of MRI and with wide availability. (See the sidebar on page 14 for ways that contrast-enhanced digital mammography is being used at MSKCC.)
Summary and Look to the Future
Vascular imaging is superior to anatomic imaging for detecting breast cancer. MRI has been well established as the most sensitive breast imaging exam, but it is expensive and not universally available. Abbreviated MRI is as accurate as standard MRI but still cannot accommodate the numbers of woman who need to be screened. Contrast-enhanced mammography finds cancers early by imaging neovascularity (like MRI) and provides a standard mammogram along with a contrast exam: all at 10% of the cost of MRI (in the United States). Contrast-enhanced mammography is also widely available, since many standard mammography machines can be upgraded for this purpose and most women prefer it over MRI, according to Dr. Jochelson.
To further substantiate the benefits of contrast-enhanced digital mammography, the prospective ACRIN CMIST trial will enroll more than 2,000 women from academic and private settings. It will compare baseline contrast-enhanced digital mammography with tomosynthesis plus screening ultrasound, with images read locally and biologic endpoints included as well.
DISCLOSURE: Dr. Jochelson has served on the speakers bureau of GE Healthcare and as a consultant to Bayer. Dr. Kuhl reported no conflicts of interest.
REFERENCES
1. Jochelson MS: Updates for vascular imaging for breast cancer detection: Abbreviated MRI and contrast enhanced mammography. 2020 Miami Breast Cancer Conference. Invited Lecture. Presented March 7, 2020.
2. Berg WA, Zhang Z, Lehrer D, et al: Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA 307:1394-1404, 2012.
3. Kuhl CK, Schrading S, Strobel K, et al: Abbreviated breast magnetic resonance imaging (MRI): First postcontrast subtracted images and maximum-intensity projection—A novel approach to breast cancer screening with MRI. J Clin Oncol 32:2304-2310, 2014.
4. Comstock CE, Gatsonis C, Newstead GM, et al: Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening. JAMA 323:746-756, 2020.
5. 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 97:37-43, 2017.
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 293:81-88, 2019.
