Breast Imaging Technologies: Early Detection Proves Critical to Survival

In 1999, the American Cancer Society estimated that 175,000 women in the United States would be diagnosed with invasive breast cancer. Forty-three thousand women were expected to die from the disease.

Early detection is one obvious way to increase survival. So, which imaging modality is best at detection? None of the technologies are fool-proof, but some modalities have proven better than others.

In the U.S., mammography is the accepted first line of defense to screen asymptomatic women for breast cancer.

“If you can only have one test, then mammography is the best to have,” advocates John Lewin, M.D., assistant professor of radiology at the University of Colorado Health Sciences Center (Denver). “Even though [mammography] will miss 15 percent of cancers that may be picked up by other tests, of any single test, it finds the most cancers.”

Kevin Kirshenbaum, M.D., director of mammography at Illinois Masonic Medical Center (Chicago) concurs. “Over the last 25 years, mammography is the No. 1 technology that has lead to a significant decrease – a 30 to 35 percent reduction – in mortality related to breast cancer.”

Conventional film-screen mammography will not find 10 to 15 percent of breast cancers for a number of reasons. Because cancers and normal breast tissues are both typically white, looking for a white tumor in a “sea of white” opaque breast tissue may make it difficult to perceive cancerous lesions.

There have been many advances in the technology of producing conventional film-screening mammograms, such as decreased radiation dose to the patient and better resolution for greater image detail. Kirshenbaum credits the American College of Radiology guidelines and standards as a major factor in the improvement of the quality of mammographic studies.

Digital Mammography
Another potential enhancement to mammographic images comes in the dawn of new digital mammography units enabled with solid-state, flat-panel detectors. In January, the first digital mammography system, the Senographe 2000D from GE Medical Systems (GEMS of Waukesha, Wis.), gained FDA regulatory clearance to begin marketing.

The digital sytem is expected to have a significant impact on reducing the number of missed breast cancers, largely due to sharper images that can be magnified and manipulated by the radiologist. Current figures estimate that 150,000 women with detectable breast cancer have a mammogram each year, but current analog technology misses cancers in 15,000 to 45,000 of them.

Edward Hendrick, Ph.D., director of breast imaging research at the Lynn Sage Comprehensive Breast Center at Northwestern Memorial Hospital (Chicago), was involved in the clinical trials conducted at the University of Colorado Health Sciences Center that lead to the FDA approval for the GEMS system.

“When you take an image with film-screen, after you process it, you’re stuck with the contrast and level of greyscales you have in the image,” Hendrick says. “With digital, you separate the acquisition process from the display process, so after the image has been acquired, you can re-display it in almost an infinite number of ways, changing the greyscales and the magnification.”

Another image enhancing quality that digital permits involves better visibility near the skin line. Hendrick explains that in a mammographic procedure with the breast compressed, there are varying layers of thickness from the center of the breast to the edges near the skin line. This characteristic translates into distortions in the greyscale analysis.

“What you can do in digital that you can’t do in film-screen, is process the image and mathematically prop up the greyscales as you go toward the skin line,” Hendrick notes.

The clinician then uses greyscales to represent real tissue differences within the breast, rather than thickness differences in the breast. This contrast resolution provides a major advantage.”

“There’s no doubt that film-screen mammography can save women’s lives,” says Etta Pisano, M.D., professor of radiology and chief of breast imaging at the University of North Carolina (Chapel Hill, N.C.) “The issue is that with digital, can we do better? From my perspective, digital has great potential.”

Pisano has been engaged in clinical trials for the past three years using a digital mammography system from Fischer Imaging Corp. (Denver). “My impression is that we will have as good or better image quality [than mammography],” she adds. “Whether that translates into finding cancers earlier has to wait until we see the data.”

Pisano notes that because of the greater cost of the equipment, digital mammography image quality must prove to be superior for that technique to supplant conventional film-screen mammography.

Robert A. Smith, Ph.D., director of cancer screening for the American Cancer Society, also believes that digital mammography will replace film-screen mammography.

“In addition to all the practical advantages of bypassing the use of film – of being able to store images on disk and transmit images from one place to another – [with digital] the radiologist has the ability to manipulate the image and suppress or bring out features to allow him or her to do a more thorough evaluation of what is initially a screening exam,” Smith says.

Although these clinicians agree that digital mammography holds the potential of improving mammographic imaging, they say the technology still should be considered as a works-in-progress.

“We also don’t want women to think that film-screen mammography is going to be inferior to digital mammography,” Hendrick adds. “Right now, a woman isn’t doing herself a disservice to get a film-screen mammogram.”

One final digital mammography issue is raised by Janet K. Baum, M.D., director of breast imaging at Beth Israel Deaconness Medical Center (Boston). “These units are going to sell for $400,000 to $500,000, while [an analog] mammography unit is somewhere around $80,000,” she notes. “Reimbursement is so low and most facilities lose money on their screening mammography.”

This era of cost containment in healthcare may dictate decisions about which imaging modality is employed for breast screening.

Ultrasound
Ward Parsons, M.D., medical director of breast imaging and clinical operations at the University of Texas Southwestern Center for Breast Care (Dallas), explains the facility uses ultrasound extensively as an ancillary diagnostic test to mammography. Ultrasound evaluates virtually every palpable mass to determine the characteristics of the abnormality.

Parsons says the facility performs approximately 75 percent of its biopsies with ultrasound guidance. Currently, the center uses Siemens Medical Systems Inc.’s (Iselin, N.J.) Sonoline Elegra with 3D. The facility plans to install the SieScape panoramic imaging to its new clinical unit soon. The facility also employs an HDI 5000 system from ATL Ultrasound (Bothell, Wash.), a Philips Medical Systems Co.

“It’s especially important to use ultrasound on the younger patient,” Parsons says. “With a 25-year-old who has a mass, we do an ultrasound to determine if it’s cystic or solid. If it is solid, [we look for] characteristics that lead us to the most probable diagnosis.”

Parsons says that at the breast care center, the radiologist handles ultrasound exams personally. The radiologist compares images from the mammogram with ultrasound images. “It’s a lot easier to do this if I’m using my hand and my eye simultaneously,” he adds.

Helen E. Mrose, M.D., Ph.D., director of breast imaging at Mercy Medical Center (Baltimore) agrees. “The reason I do ultrasound myself, rather than have a technologist do it, is that I believe breast ultrasound is one of the most difficult imaging modalities. It is a very experience related, real-time exam,” she continues. “You may notice a cyst and fail to notice there is something right next to it, so you must be present when the scan is done. If we find a lesion on ultrasound, I can aspirate right there.”

Kirshenbaum relates that clinical studies suggest yet another role for ultrasound in breast imaging. Besides evaluating cysts and solid masses, researchers advocate using ultrasound to differentiate solid lesions, grouping them into those that are benign and those that cannot be considered benign. In any situation, they are lesions that should be biopsied.

Louis J. Perl, M.D., of Overlook Hospital (Summit, N.J.) uses ultrasound guidance with the Mammotome breast biopsy system from Ethicon Endo-Surgery to perform minimally invasive breast biopsies.
Photo: Ethicon Endo-Surgery

Louis J. Perl, M.D., an attending radiologist at Overlook Hospital (Summit, N.J.), uses ultrasound guidance via a hand-held Mammotome breast biopsy system from Ethicon Endo-Surgery Inc. (Cincinnati), a Johnson & Johnson Co. (New Brunswick, N.J.), to perform minimally invasive, vacuum-assisted breast biopsies.

Perl says he has performed hundreds of stereotactically guided Mammotome biopsies. Overlook is the first and currently the only hospital in New Jersey using ultrasound guidance to perform this procedure, which requires an incision about a quarter of an inch in size.

“I don’t think this is the only thing to be done,” Perl says. “I respect my colleagues who do core biopsies. I do think this is easier and faster.” Typically, this procedure takes only an hour to accomplish and the patient goes home with a Band-aid over the tiny incision.

Magnetic Resonance Imaging (MRI)
From a practical standpoint, MRI is not expected to become a screening modality for breast cancer. This form of imaging is expensive and there are time limitations on access to the equipment.

“If you want to screen 125 million women in the United States, it’s going to be tough to get them in and out of MRI machines,” says Kirshenbaum. However, for several specialized applications, MRI can prove beneficial.

“There are some cases, where additional imaging, like MRI, can be extremely useful,” says Jennifer A. Harvey, M.D. associate professor of radiology and director of the division of breast imaging at the University of Virginia (UVa of Charlottesville, Va.). “For instance, if a patient has a new inverted nipple that has developed, MRI could find a retroareolar cancer that was not evident in any other way.”

MRI also has proven helpful in evaluating the extent of breast disease. “Cancer is quite frequently multifocal and we only see it in primary lesion on mammography or sonography,” continues Harvey. “You do the MRI and find out there’s multifocal disease. Usually it’s located in the same quadrant, but we’ve had two cases in the last year in which there was a second focus of cancer in a different quadrant of the breast. That usually means the patient is no longer a lumpectomy candidate.”

MRI is beneficial in planning surgical intervention and in evaluating chemotherapeutic treatment. “MRI is useful to assess for chest wall invasion [of a cancer lesion], because that really changes how they treat the patient,” Harvey says. “If there is a cancer in the posterior aspect of the breast, if it invades the pectoralis muscle, the patient usually gets chemotherapy before surgery. If they go in without knowing the chest wall is involved, it delays chemotherapy, but then also the patient will need radiation to the chest wall.”

“My focus is to harness this technology to solve clinical problems,” explains Laura Esserman, M.D., M.B.A., director of the Carol Franc Buck Breast Care Center at the University of California at San Francisco (San Francisco).

In the research she completes with colleagues, the UCSF team uses MRI for staging tumors to determine the extent of DCIS (ductal carcinoma in situ) and to organize therapeutic response to malignancy management.

One area of investigation involves the use of MRI to determine tumor response to chemotherapy. “The thing we know about new chemotherapy is if your tumor goes away, your chance of survival is probably 90 percent. If it doesn’t, your survival chance is closer to 20 to 30 percent. This immediately stratifies you,” Esserman explains. “If we can sort out how to type the tumor by imaging, it may be that we can tell in stage one or two (when we cannot see them so well) and it may help to classify these lesions.”

This capability expands treatment options and allows evaluation of chemotherapeutic agents currently in development.

Positron Emision Tomography (PET)
PET is a functional imaging modality because the test evaluates functional processes in the body, as compared to other modalities, such as MRI, ultrasound or mammography which provide anatomical images. Although currently part of the routine clinical care for other cancer patients, breast cancer exams using PET currently are not covered by Medicare. However, by this summer, reimbursement could become a reality.

“In PET, we use radioactively labeled sugar injected into the vein,” explains Johannes Czernin, M.D., director of nuclear medicine at the University of California-Los Angeles (UCLA) Medical Center. “It accumulates into tissue that consumes a lot of sugar.”

That includes normal brain and heart tissues. Tumors consume a large amount of sugar, because they have an incredible growth rate. This condition provides the mechanism for visualizing tumors with PET.

“When we look in the literature about PET studies for breast cancer, many studies show overall accuracy of 85 to 100 percent,” Czernin adds. “It also can be used to stage the axilla for lymph node involvement and whole-body tests to look for distant metastases.”

Laser CT trials
The University of Virginia has one of two laser CT breast imaging devices in the country.

Harvey describes the device as similar to a stereotactic table where the patient lies prone, with the breast to be examined placed into a scanning chamber with no compression. The laser used to generate an image rotates completely around the breast (360 degrees) and takes slices at three-millimeter intervals. The data is reconstructed in basically a 3D image. The technique allows the clinician to review images in any plane, axial, coronal or sagittal.

“Different objects in the breast have different refractal properties,” Harvey notes. “Primarily at this wave length, the laser gets absorbed by blood. Areas that have increased vascularity, like tumors, should show up on these images.”

Harvey is using equipment manufactured by Imaging Diagnostics Systems Inc. (Plantation, Fla.).

“At this point, we’re still learning how to read these, but so far it looks like fibrocystic change will not present a false positive.” Harvey says. “This will differentiate this technique from others like ultrasound and mammography. We don’t know yet what the sensitivity and specificity of this test will be, because we haven’t studied it enough yet.”

Scintimammography
Scintimammography is a nuclear medicine scan that some physicians utilize in evaluation of breast lesions in patients who have an abnormal mammogram or palpable breast mass.

For this imaging technique – which costs between $400 and $600 – the patient receives an intravenous injection of a radioactive tracer (Technetium Tc99 Sestamibi). One such tracer is Miraluma from DuPont Pharmaceuticals Co. (Wilmington, Del.).

The patient lies in a prone position on the imaging table equipped with a gamma camera to provide several images of the breast tissue. The quantity and position of the tracer detected by the camera demonstrates blood flow within the breast. Increased blood flow may indicate the presence of a tumor.

Some clinicians have found scintimammography a useful adjunct to mammograms, especially in women with dense breasts or those who have undergone one or more breast biopsies. The resulting scar tissue make future interpretation of mammograms more complicated.

“We’ve done more than 800 Miraluma examinations in our office,” says Steven L. Edell, D.O., FACR, medical director of the Women’s Imaging Center of Delaware (Newark, Del.) “The most significant indication we have is when a patient comes in with a palpable mass that we don’t see mammographically or on ultrasound. It’s the patient who has an equivocable mass.”

When the center is unsure if the patient has a malignancy or just normal glandular hormonally active breast tissue, scintimammography with Miraluma has proven beneficial. Edell’s facility served as a primary site in the FDA clinical trials for Miraluma leading to its approval for use in breast cancer diagnosis.

“The next most common area is when we see something mammographically, but we’re not sure it really exists, [such as] an asymmetric density with a questionable mass next to it,” Edell says. After an ultrasound exam is performed, if the lesion cannot be visualized, scintimammography becomes the next option.

Daniel Kopans, M.D., professor of radiology at Harvard Medical School (Cambridge, Mass.) and director of the breast imaging division at the Massachusetts General Hospital (Boston, Mass.), expresses reservations about the value of scintimammographic examinations.

His division also was involved in the FDA clinical trials for Miraluma. He notes concerns about methodology used in the research.

“The sensitivity and specificity in that study were quite good, but the radiologists weren’t blinded to the other information,” he says. “You don’t know whether it was the scintimammography that was good or the combination of everything together [including mammograms performed as part of the study].”

Kopans suggests that given other diagnostic techniques – such as needle biopsies and surgical biopsies that are performed as outpatient procedures – scintimammography will not add information that is not available through other imaging methods.