New technology to supplement digital mammography may improve breast cancer screening and diagnosis. Although some of these new imaging modalities are still under development, others are already in clinical use as adjuncts to mammography for breast cancer screening and staging.
The current standard of care for breast cancer screening is digital mammography, a time-tested modality that has helped save countless lives. But women with dense breasts or genetic risk factors require additional imaging, usually with ultrasonography or breast magnetic resonance imaging (MRI). These modalities are also used for clinical staging.
However, the current standard imaging techniques have limitations that can impair their effectiveness as screening and staging tools. Therefore, researchers at The University of Texas MD Anderson Cancer Center and elsewhere are exploring new imaging modalities to determine which techniques are appropriate for which uses.
Tomosynthesis, also called three-dimensional (3D) mammography, is performed with an x-ray scanner that moves in an arc over the breast. In a few seconds, this technique obtains up to 60 images of the breast rather than the one or two images that would be obtained with the stationary scanner used for standard digital mammography. Tomosynthesis has experienced rapid growth over the past 2 years and is available for breast cancer screening at many centers.
“Tomosynthesis is an important addition for breast cancer imaging,” said Basak Dogan, M.D., an associate professor in the Department of Diagnostic Radiology’s Breast Imaging Section. “It’s used in conjunction with standard mammography for routine screening, where it helps eliminate tissue overlap that obscures masses.”
A retrospective analysis of 13 single-institution studies in which tomosynthesis was added to mammography for routine screening found that the addition of tomosynthesis resulted in a significant increase in the number of invasive cancers identified. The study, which was published in June 2014 in The Journal of the American Medical Association, also found that tomosynthesis significantly reduced the number of women who were recalled for additional testing because of abnormal findings on mammography. Dr. Dogan said, “Avoiding unnecessary recall spares patients the anxiety of undergoing additional testing for a suspected cancer and saves patients and insurance companies the cost of those tests.”
Dr. Dogan added that tomosynthesis is also under investigation as a staging tool. “Dr. Rosalind Candelaria here at MD Anderson is leading an ongoing clinical trial to see if tomosynthesis will improve the accuracy of staging breast cancers,” Dr. Dogan said. “We want to see if we will find additional tumors with tomosynthesis that regular mammography doesn’t catch and how many cancers it will catch in the contralateral breast.”
Other possible uses for tomosynthesis remain to be explored. Dr. Dogan said, “Ultrasonography is currently used to supplement screening mammography in women with dense breasts, and it’s not clear whether ultrasonography is still needed when tomosynthesis is used. This needs to be studied further.”
Dr. Dogan said that the main concern patients and physicians have about adding tomosynthesis to screening mammography is the additional radiation exposure. Each tomosynthesis image carries the same low effective dose of ionizing radiation (0.7 mSv) as a standard 2D mammography view, so although performing both techniques using separate scanners doubles the dose to the patient, this dose remains low and is not thought to add to a patient’s lifetime cancer risk. Still, to keep the screening radiation dose as low as possible, new software (C-View, Hologic) allows tomosynthesis scanners to obtain 2D mammograms at the same time as 3D images, thereby keeping the dose approximately the same as that of either scan performed alone. Dr. Dogan said several scanners at MD Anderson will be upgraded with this software by the end of this summer.
Molecular breast imaging
Molecular breast imaging (MBI) is a new imaging technique that can be used as an adjunct to traditional mammography. In a recent screening trial in women with dense breast tissue, the cancer detection rate increased from 3 to 12 cancers per 1,000 women when MBI was added to mammography, said Gaiane Rauch, M.D., Ph.D., an assistant professor in the Department of Diagnostic Radiology’s Body Imaging Section.
MBI uses technetium-99m, a short-lived radioactive tracer that is injected intravenously, after which the breasts are scanned with gamma cameras. The patient is comfortably seated with the breasts lightly compressed while undergoing MBI. “A mammogram gives an anatomical image,” said Beatriz Adrada, M.D., an associate professor in the Department of Diagnostic Radiology’s Breast Imaging Section. “MBI gives a functional image; tumors take up the radiotracer.”
Dr. Rauch added that radiologists compare the images from mammography and MBI side by side. “Sometimes in patients with dense breast tissue, you cannot see an abnormality on mammography,” she said. “The lesion is hiding behind the dense breast tissue. On MBI, you can see the lesion standing out. It lights up.” Drs. Rauch and Adrada said that MBI offers a significant advantage over ultrasonography as a supplemental screening modality because MBI can be interpreted rapidly and has fewer false-positive findings, which lead to unnecessary biopsies.
Several studies have found that the sensitivity of MBI and contrast-enhanced breast MRI are similar, but the specificity of MBI is better, decreasing the number of false-positive findings. Another advantage of MBI over MRI, Drs. Rauch and Adrada said, is that MBI is more comfortable for claustrophobic patients and is not contraindicated in patients with metallic implants or renal disease. The lower cost of MBI is an additional advantage over contrast-enhanced breast MRI.
Researchers also want to know whether MBI can help gauge treatment response. Dr. Rauch is the principal investigator of a study in which patients undergo MBI after receiving two cycles of neoadjuvant chemotherapy. “The goals of the study are to see if MBI can predict the treatment response to neoadjuvant chemotherapy in patients with invasive breast cancer and help surgeons evaluate residual disease before surgery,” she said.
As with tomosynthesis, some physicians and patients are concerned about the radiation dose from MBI. However, Drs. Rauch and Adrada said the radioactivity from the amount of technetium-99m used in MBI is only 8 mCi (296 MBq), with an effective dose of 2.4 mSv. Although this is higher than the average effective dose from digital mammography combined with tomosynthesis, this effective dose is below the average annual dose of natural background radiation (3 mSv). By comparison, the radioactivity from the amount of technetium-99m used in a cardiac nuclear stress test can be as high as 30 mCi (1,110 MBq).
Other new imaging techniques
While tomosynthesis and MBI are among the more promising new modalities for breast imaging, other new techniques are also under investigation. One such technique is automated breast ultrasonography. Dr. Dogan said, “Automated breast ultrasonography can obtain the same images as classic hand-held ultrasonography in half the time: 20 minutes as opposed to 40. We hope to offer it to patients with dense breasts as a supplemental screening method.”
Another investigational imaging technique is optoacoustic, or photoacoustic, imaging. Optoacoustic imaging uses a pulse of light to heat tissue slightly; the heated tissue generates sound waves that produce functional images similar to MBI, with superimposed ultrasonograms.
Dr. Dogan is the institutional principal investigator of an ongoing study investigating the role of optoacoustic imaging in distinguishing benign breast masses from malignant masses. The study has completed patient accrual, and the results are being analyzed for publication. She added that in another multi-institutional trial, her colleagues are obtaining optoacoustic images through a tomography-based device. “This technique lets us obtain aerial views of the entire breast, not just a lesion, and tell whether any site requires biopsy,” she said.
Dr. Dogan is also the principal investigator of a clinical trial of microbubble-based imaging of the lymph nodes. “This trial involves finding the sentinel lymph nodes using intradermal microbubble contrast under ultrasound guidance,” she said. “The microbubbles are perflutren gasses surrounded by phospholipids. Those air bubbles in the lymphatic channels make the contrast agent visible. This allows us to find the sentinel lymph node and do a needle biopsy—potentially eliminating the need for the surgeon to find and remove the sentinel lymph node.” Dr. Dogan added that MD Anderson is the first center in North America to use this technique.
Another technique under investigation is not a new modality but one that is usually not applied to breast imaging: diffusion-weighted MRI. Traditionally, contrast-enhanced MRI is used in breast imaging. However, Dr. Dogan is the principal investigator at MD Anderson for a multi-institutional trial in which patients who undergo contrast-enhanced breast MRI also undergo diffusion-weighted imaging. “We’re comparing the two sets of images, and we’re finding that lesions that take up contrast agent but appear benign on diffusion-weighted MRI wind up being benign on biopsy,” Dr. Dogan said. “The limitation of diffusion-weighted MRI is that it misses smaller tumors. I believe that as technology improves, we will overcome this limitation.” She added that the advantage of diffusion-weighted MRI is that the scan is quick and easy to add to any MRI protocol.
Obstacles and opportunities
The use of new imaging techniques can be limited by their cost. Dr. Rauch said that although MBI can be done at half the cost of breast MRI, patients undergoing screening with MBI may face problems with insurance reimbursement. “For a patient with cancer, MBI for staging is likely to get reimbursed; but for screening, reimbursement can be an issue because MBI is a new modality,” she said.
Dr. Dogan said that insurance companies have similar reservations about covering tomosynthesis for breast cancer screening. To avoid possible hardship for patients owing to insurance denial, MD Anderson charges a standard $60 fee for screening tomosynthesis. “Reimbursement by insurance companies is spotty for screening tomosynthesis because there are not yet any data to show that the procedure has an effect on mortality,” she said. “It’s an extremely new technology that came to the playing field only 2 years ago, so there won’t be any survival data for another 8–10 years.”
Dr. Dogan added that she is confident that screening tomosynthesis will prove to have a survival benefit. “There’s still room for improvement, and there are still unanswered questions,” she said. “But I think tomosynthesis is farther along than the other new technologies. It’s almost resulted in a paradigm shift in screening.”
For more information, contact Dr. Beatriz Adrada at 713-792-2709, Dr. Basak Dogan at 713-563-0124, or Dr. Gaiane Rauch at 713-745-5768.
OncoLog, June 2015, Volume 60, Issue 6
Breast Cancer Screening Guidelines
Physicians at MD Anderson follow the American Cancer Society’s recommendation that women 40 years or older undergo annual screening mammography. Breast cancer screening guidelines, patient risk assessment charts, and a physician breast cancer screening algorithm are available at www.mdanderson.org/patient-and-cancer-information/cancer-information/cancer-topics/prevention-and-screening/screening/breast.html.