 Gadolinium-enhanced maximal intensity projection (MIP) subtraction breast MRI, axial (top) and oblique (bottom) views, reveal unsuspected multi-centric tumors in a 46-year-old woman with a negative mammogram, dense breast, and fine needle biopsy of a lump at 12:00, positive for malignant cells in the right breast. Arrows indicate known carcinoma. Images provided by Bruce Porter, MD, First Hill Diagnostic Center, Seattle. |
Mammography saves lives. Any remaining doubt should have been erased by an article published this spring1 demonstrating a 63% reduction in mortality with regular screening. A computer model suggests that biannual screening might reduce mortality as much as 80%,2 although others argue that twice-a-year mammography would not be cost-effective.
What of the full-screen digital study? Studies continue to show that digital and film-screen studies are equally accurate,3 putting pressure on imaging centers to avoid buying the expensive equipment. However, full-screen digital studies may reduce the number of recalls,3 and they open the door to techniques that might save money and lives, including computer reading of the images and telemammography.
The Electronic Mammographer
The Food and Drug Administration has approved a system for what is often called “computer-aided diagnosis” but is more accurately called “computer-aided detection (CAD).”
Hans Ringertz, MD, PhD, professor and chairman of the Department of Radiology at the Karolinska Institute in Stockholm, has discussed the application of CAD in mammography.
“In 4% of all diagnostic imaging evaluations, we make mistakes,” he said. “About half of these mistakes do not matter, but in a fraction of 1%, they are catastrophic. The CAD systems help prevent you from making obvious mistakes. The beauty of CAD is that the machine never gets sleepy, it never gets bored, and it never comes to work with a hangover!”
The Elizabeth Wende Breast Clinic in Rochester, NY, which does 65,000 mammograms a year, recently began a prospective study of 35,000 patients. Kathleen Willison, RT, the clinical study manager, described the goals.
“We routinely double read mammograms, because it is more sensitive,” she notes. “We want to determine how CAD fits into double reading and whether one radiologist using CAD can approach the accuracy of two radiologists. Our expectations are that the findings of CAD combined with the radiologists will dovetail to produce a higher sensitivity.”
How easily does CAD join a mammography practice?
“There is a learning curve,” Willison stresses. “Also, initially, the radiologist may compete with the unit, but that attitude fades. Most radiologists appreciate the help, especially when they are reading alone and do not read a large number of mammograms.”
Mammography has been a prime focus of teleradiology, both to make mammography more convenient by permitting images to be obtained at sites removed from a clinic and to provide service to women with poor access to health care. With the availability of full-field digital mammography, the Department of Defense, the Office on Women’s Health, and the National Cancer Institute have fielded a Mobile Breast Care Center (MBCC) with integrated satellite communications facilities. In a 15-month trial sponsored by the Susan G. Komen Breast Cancer Foundation, the MBCC van will screen approximately 2,000 Navajo women on a reservation in Arizona. The images will be transmitted to Walter Reed Army Medical Center in Bethesda, Md, for interpretation while the women are still in the van.
Great Utility, Poor Reimbursement
The traditional concept of breast ultrasonography is that it does no more than distinguish a cyst from a solid mass. This is an antiquated view of ultrasonography’s capabilities, according to Bruce A. Porter, MD, medical director of First Hill Diagnostic Center in Seattle. Nevertheless, third-party payors adhere to it and reimburse accordingly, often paying less than the facility’s cost of doing the study. Therefore, many imaging practices still use old scanners because it does not make economic sense to buy a state-of-the-art system.
Among the capabilities now offered is real-time spatial compounding. Instead of emitting one straight beam, this scanner sweeps a beam over a 30-degree arc, acquiring as many as nine images at different angles and registering them in real time. The signal-to-noise ratio and resolution are markedly enhanced, allowing the radiologist to examine the internal architecture of structures as small as 3 mm. The newer scanners also have Doppler capabilities, which can help differentiate postoperative and postradiation scarring from residual or recurrent cancer.
“We could significantly reduce the number of breast biopsies by about 20% if modern ultrasonography equipment were used more widely,” Porter stresses, “and we could do wire localizations and biopsies on much smaller and potentially curable lesions.”
Porter is concerned that few mammographers are trained in ultrasonography and thus may fail to recognize clear malignant findings. He remembers a case in which a veil-like shadowing on the sonogram was thought to be fibrocystic change. Six months later, the woman returned with an inflammatory lobular stage T4 cancer.
“Even though she is likely to die from this tumor, this disease was detectable earlier,” he points out.
Mammography is notoriously poor at defining the histologic extent of a cancer, and as many as 50% of lumpectomy specimens have positive or inadequate margins. To avoid leaving tumor behind, the patient undergoes a second resection. In an attempt to improve breast-conserving procedures, a team in Charlottesville, Va, used intraoperative ultrasonography to guide the resection.4 The imaging improved the status of the margins without increasing the cost of the surgery.
Nuclear Possibilities
.jpg) Gadolinium-enhanced maximal intensity projection (MIP) subtraction breast MRI, axial (top) and oblique (bottom) views, reveal unsuspected multi-centric tumors in a 46-year-old woman with a negative mammogram, dense breast, and fine needle biopsy of a lump at 12:00, positive for malignant cells in the right breast. Arrows indicate known carcinoma. Images provided by Bruce Porter, MD, First Hill Diagnostic Center, Seattle. |
Nuclear medicine may have applications in the evaluation of breast lesions and staging of the axilla. Radiologists from Los Robles Medical Center in Thousand Oaks, Calif, presented a prospective study of scintimammography in 75 patients with minimal mammographic and clinical findings.5 Of the 30 cancers, 27 produced a defined focus of tracer uptake. Significantly, eight of the lesions were not palpable and were not seen by mammography, and 11 were smaller than 1 cm. Other studies confirm the utility of scintimammography both for determining the nature of a breast lesion and for identifying local metastases.6-9
Positron emission tomography (PET) has great appeal because it depicts chemistry as well as anatomy. With fluorodeoxyglucose (FDG) as the tracer, the radiologist can identify areas with greater metabolic activity, a common feature of cancer. Can PET determine whether a breast lesion found on mammography is benign or malignant?
“Positron emission tomography has been advocated as perhaps the most sensitive and specific examination one could apply to the breast,” reports Yuri Parisky, MD, chief of Breast Imaging Services at the University of Southern California Norris Comprehensive Cancer Center. “The problem is that it is too expensive: $1,600 to $2,100.10 A biopsy is probably cheaper.”
There is greater agreement about the value of PET for detecting metastases and for treatment planning.
“I recently saw a patient with advanced local disease. What kind of chemotherapy is appropriate: should it be aggressive, or should it be maintenance? To answer that question, you need to know whether she has metastatic disease and, if so, how much disease she has.”
An often-cited study on PET utility, reported last June at the 47th Annual Meeting of the Society of Nuclear Medicine in St Louis, surveyed referring oncologists managing 40 women with breast cancer. The PET images showed 21% of the women to have more disease than had been found by other methods. According to Johannes Czernin, MD, director of nuclear medicine at UCLA Medical Center and the lead investigator, “what is significant is that PET was instrumental in altering treatment in more than 20% of the patients.”
There remains a considerable reluctance to use PET perhaps largely because of the cost. In June 2001 there were two important developments in PET for breast imaging. First, the Blue Cross and Blue Shield Technology Evaluation Center completed a government-funded study of the modality. The center found no studies demonstrating that PET imaging is valuable in patients with less suspect mammographic findings or that PET imaging improves clinical outcomes. Later in the month, the Medicare Coverage Advisory Committee on Diagnostic Imaging Panel heard presentations from members of the Society of Nuclear Medicine, the American College of Radiology, and the Academy of Molecular Imaging (formerly the Institute for Clinical PET) as it considered whether to recommend Medicare reimbursement for five potential PET uses.
One of the presenters was Peter Conti, MD, director of the PET Imaging Science Center and associate professor of radiology, clinical pharmacy, and biomedical engineering at the University of Southern California. He noted that PET is invaluable in patients with advanced disease, especially when additional chemotherapy is being considered, and that it is superior to CT and MRI in this situation. He also reported that PET is valuable in women with dense or surgically manipulated breasts, in whom mammography often is limited.
“We believe that the studies prove, and physicians’ experience shows, that PET is a proven diagnostic tool,” Conti stresses.
The committee initially rejected all five indications for reimbursement by the Centers for Medicare and Medicaid Services (formerly HCFA). However, the committee eventually accepted PET as an adjunct to standard staging tests to detect locoregional recurrence or distant metastases or recurrence. Coverage could begin next year.
Parisky suspects that further technological developments will force another look at PET for the breast. Some companies are working on stand-alone small PET scanners for the breast or putting small cameras on mammography equipment for what is called “positron emission mammography.” In one small trial,11 subjects with suggestive mammographic findings or a palpable mass underwent the study, which takes no more than 5 minutes. As judged by the histologic findings, the sensitivity of PET was 80%, the specificity was 100%, and the accuracy was 86%.
What are the Uses of MRI?
.jpg) Core biopsy in a 55-year-old woman with palpable lump but indeterminate mammogram revealed lobular carcinoma, size uncertain. MRI detected malignant enhancement on dynamic 3-D contrast-enhanced study of 5.5-cm diameter (a). Color-enhanced image increases conspicuity of diffusely infiltrative tumor (b). Ultrasound showed diffuse nonfocal shadowing both with conventional ultrasound (c) and real-time spatial compound imaging (d). Images provided by Bruce Porter, MD, First Hill Diagnostic Center, Seattle. |
First Hill Diagnostic Center has done more than 900 bilateral contrast-enhanced breast MRI studies and has defined eight indications. One is to evaluate the extent of lobular carcinoma, which tends to be multifocal and bilateral and may be invisible on the mammogram, particularly in a dense breast. A second is to examine a woman for multiple or bilateral cancer and a third is to distinguish scar from recurrent tumor.
The first use Porter made of breast MRI was to find an occult primary tumor in a woman with tumor-involved lymph nodes.
“In the past, this situation usually dictated mastectomy,” Porter points out. With MRI, his team has been able to find the primary lesion in about two thirds of the patients, who thus became candidates for breast-conserving surgery.
The correlation between the dimensions of the abnormality on the MRI images and the pathology findings is excellent, so some centers, particularly in Europe, use breast MRI preoperatively to reduce their reoperation rates. In the United States, this practice is not routine because a breast MR examination costs $1,000 or $1,200. However, a second resection costs $3,000 to $5,000.
Another current indication for MRI is monitoring of neoadjuvant chemotherapy. A dynamic study is obtained before treatment begins and at intervals thereafter. A bolus injection of contrast medium is given, and a series of images is acquired at 1-minute intervals from which enhancement curves are constructed. With successful neoadjuvant chemotherapy, the enhancement curves change significantly as the cancer dies and its blood flow declines.
Chemotherapy monitoring also has been done by PET, and there are not enough data comparing the two modalities for this indication. PET has an edge because of its ability to document the metabolism of the tumor, but MRI is superior in determining size, extent, and number of lesions.
Young women treated for high-grade lymphomas during adolescence have an exceedingly high incidence of breast cancer. Mantle radiation seems to be the principal predisposing factor, but a few affected patients received only chemotherapy.
.jpg) A 68-year-old woman with silicone implants, redness, and edema of the left breast and axilla, suspected to be acute rupture. Noncontrast breast MRI revealed intact implant with spiculated mass adjacent. Ultrasound showed malignant-like mass with increased vascularity on Doppler, and core biopsy revealed inflammatory lobular carcinoma. Images provided by Bruce Porter, MD, First Hill Diagnostic Center, Seattle. |
“We have seen a number of these women with cancers and negative mammograms,” Porter says. “This group and women with the ‘breast cancer gene’ are populations for which we should consider early screening. As an adjunct to mammography and physical examination, MRI is a very powerful tool in this situation and may help the women avoid bilateral mastectomy.”
More women with breast implants are entering the peak age group for breast cancer. As has been widely reported, mammography is not always useful in this situation, and physical examination of the breast can be difficult. Again, MRI (or ultrasound) may be helpful.
“When a woman with implants has swelling of the breast, it is foolish to assume, as is often done, that it is mastitis or an acute episode of fibrous contracture. You always have to think of inflammatory cancer, as it is impressive how quickly these lesions can kill if you do not identify them early,” Porter notes.
Some New Methods
Many years ago, considerable money was spent trying to differentiate benign and malignant breast lesions by measuring temperature via thermography. The effort grew from the realization that cancers tend to be hotter than normal tissue.
Thermography never became a routine clinical modality. Today, with our greater understanding of tumor neovascularity and better technology, thermal imaging with computer analysis shows promise.
Parisky, the principal investigator for the major trial of a system under review by the FDA, explains why this new technique may well succeed where thermography failed.
“When cool air is blown over tissue, normal blood vessels constrict. However, the blood vessels induced by a cancer generally do not respond to a vasoconstrictive stimulus. Computer analysis of these temperature data will enable radiologists to make better decisions and decrease the number of biopsies that produce benign tissue.”
Another of the new techniques is electrical impedance scanning, which detects differences in the conductivity of normal and malignant tissue. This technique is in the early stages of development as an adjunct to mammography. According to some investigators, it is more sensitive than ultrasonography but inferior to MRI.12
Conclusion
Mammography is the greatest tribute to the idea that regular imaging can detect a lethal disease in time to save the patient’s life. However, as long as it is not 100% sensitive and 100% specific, efforts will continue to develop adjunctive methods of examining the breast.
Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.
References:
- Tabar L, Vitak B, Tony HH, Yen MF, Duffy SW, Smith RA. Beyond randomized controlled trials: organized mammographic screening substantially reduces breast carcinoma mortality. Cancer. 2001;91:1699?1703.
- Michaelson JS, Halpern E, Kopans DB. Breast cancer: computer simulation method for estimating optimal intervals of screening. Radiology. 1999;212:551?560.
- Lewin JM, Hendrick RE, D?Orsi CJ, et al. Comparison of full-field digital mammography with screen-film mammography for cancer detection: results of 4,945 paired examinations. Radiology. 2001;218:873?880.
- Moore MM, Whitney LA, Cerilli L, et al. Intraoperative ultrasound is associated with clear lumpectomy margins for palpable infiltrating ductal breast cancer. Ann Surg. 2001;233:761?768.
- Polan RL, Klein BD, Richman RH. Scintimammography in patients with minimal mammographic or clinical findings. Radiographics. 2001;21:641?655.
- Melloul M, Paz A, Ohana G, et al. Double-phase 99mTc-sestamibi scintimammography and trans-scan in diagnosing breast cancer. J Nucl Med. 1999;40:376?380.
- Buscombe JR, Cwikla JB, Holloway B, Hilson AJW. Prediction of the usefulness of combined mammography and scintimammography in suspected primary breast cancer using ROC curves. J Nucl Med. 2001;42:3?8.
- Wong JH, Steinemann S, Ko PJ, Wong DL. The value of breast lymphoscintigraphy in breast sentinel node staging. Clin Nucl Med. 2001;26:502?505.
- Lumachi F, Ferretti G, Povolato M, et al. Usefulness of 99m-Tc-sestamibi scintimammography in suspected breast cancer and in axillary lymph node metastases detection. Eur J Surg Oncol. 2001;27:256?259.
- Keppler JS, Conti PS. A cost analysis of positron emission tomography. AJR Am J Roentgenol. 2001;177:31?40.
- Murthy K, Aznar M, Thompson CJ, Loutfi A, Lisbona R, Gagnon JH. Results of preliminary clinical trials of the positron emission mammography system PEM-1: a dedicated breast imaging system producing glucose metabolic images using FDG. J Nucl Med. 2000;41:1851?1858.
- Malich A, Boehm T, Facius M, et al. Differentiation of mammographically suspicious lesions: evaluation of breast ultrasound, MRI mammography and electrical impedance scanning as adjunctive technologies in breast cancer detection. Clin Radiol. 2001;56:278-283.
