Because of the immense burden of cancer, and the inherent limitations of mammography, the search for more effective technologies for early breast cancer detection has been intensified. In 1999, the Institute of Medicine (IOM) undertook an evaluation of technologies and practices in the early detection of breast cancer by empanelling a committee of 16 with expertise in breast cancer, medical imaging, cancer biology, epidemiology, economics, and technology assessment. The committee examined the peer-reviewed literature, met four times, held two workshops that dealt with new technologies as well as policies related to their adoption and dissemination, and consulted with experts in the field.
The study results were first announced in March 2001, and the printed version of the final report, “Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer,” recently became available.
Early detection and improved treatment have likely contributed to a 2% annual decrease in breast cancer deaths for American women over the past decade. But despite those gains, breast cancer remains the second leading cause of death from cancer among women in the United States, killing more than 40,000 women each year. New imaging and molecular biological technologies are being developed to detect and diagnose the disease at an early stage.
Although several new technologies show promise for improved capability to detect breast cancer, none has yet proved superior to traditional, x-ray film mammography in screening for breast cancer, says the IOM report. More evaluation and development of new imaging tools and of promising molecular biological techniques are required and warranted.
“With all of its limitations, film mammography remains the gold standard against which new imaging technologies will be measured,” said Joyce C. Lashof, chair of the IOM committee that wrote the report and professor emerita, School of Public Health, University of California, Berkeley. “To date, no quantum leap has been made in this area. At the same time, many of the newer tools offer certain advantages and deserve to be studied further.”
IOM Committee Findings
Early detection is widely believed to save lives by facilitating intervention early in the course of the disease, at a stage when cancer treatment is most likely to be effective. This concept, however, belies a number of complexities. Clinical trials have demonstrated that x-ray mammography screening can detect many cancers at an earlier stage than they would otherwise be found, and can reduce breast cancer deaths. Among women who were routinely screened by mammography in clinical trials, fewer women died from breast cancer-as much as 30% fewer compared to unscreened women. A recent report from Sweden found regular mammographic screening resulted in a 63% reduction in breast cancer deaths among women who actually underwent screening.
The IOM Mission
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The mission of the Institute of Medicine is to advance and disseminate scientific knowledge to improve human health. The Institute provides objective, timely, authoritative information and advice concerning health and science policy to government, the corporate sector, the professions, and the public.
But screening mammography cannot eliminate all deaths from breast cancer because it does not detect all cancers, including some that are detected by physical examination. Mammograms are particularly difficult to interpret for women with dense breast tissue, which is especially common in younger women. Dense tissue interferes with the identification of abnormalities associated with tumors, leading to a higher rate of false test results among these women. Some tumors may also develop too quickly to be identified at the most curable stage using the standard screening intervals.
Breast cancer screening also entails risk of false-positive results, overdiagnosis, and overtreatment. Of all breast lesions that are biopsied as a result of suspicious findings on a mammogram, as many as three-quarters turn out to be benign. “Overdiagnosis” means that small lesions are sometimes determined to be cancerous or precancerous when in fact the lesions might never have developed into a life-threatening disease if they had been undetected and left untreated. In such instances, some of the supposed “cures” following early detection by screening may not be actual cures, and thus, these women are unnecessarily treated. All of these factors must be taken into consideration when making policy decisions about screening programs.
The IOM Report-Where to Find It
Committee on Technologies for the Early Detection of Breast Cancer, Sharyl J. Nass, I. Craig Henderson, and Joyce C. Lashof, Editors, National Cancer Policy Board, Institute of Medicine, Division of Earth and Life Studies, National Research Council. Mammography and Beyond: Developing Technologies for the Early Detection of Breast Cancer. (Available on-line at http://books.nap.edu/catalog/10030.html)
The committee evaluated imaging tools that are currently available, examining film mammography and 17 other technologies. These included ones with Food and Drug Administration (FDA) approval, such as full-field digital mammography, ultrasound, computer-aided detection systems, and magnetic resonance imaging, as well as those not yet approved, such as optical imaging. Many appear to offer varying degrees of potential for screening or diagnosis-in some cases, both-but more research is needed. No studies have shown a new technology to be a replacement for film mammography, for either screening or diagnosis. For instance, while digital mammography has been lauded as a major technical advance-facilitating storage, retrieval, transmission, and adjustment of images for mammograms-it has not shown greater accuracy than its nondigital counterpart. Several show promise as adjuncts to mammography, but to date, none has been proved to be superior to conventional mammography for routine screening. Ultrasound and MRI can aid in diagnosis and may be of value in screening selected groups of women. Many other new technologies are at a relatively early stage of development, and thus more research is needed to adequately assess their accuracy and effectiveness.
Introducing Tumor Biology
Traditional imaging technologies identify cancers based on structural abnormalities, but some of the newer imaging methods attempt to identify biological changes as well. In addition, many new technologies that are not based on imaging are being developed and have potential for screening or diagnostic applications. For example, some of the latest molecular biological technologies can provide information about the genetic and cellular characteristics of these abnormalities.
The key to overcoming overdiagnosis and overtreatment associated with cancer screening may lie in better discrimination of lesions based on new knowledge in basic tumor biology. Technical improvements in breast imaging techniques have led to an increase in the rate of detection of small, early lesions, such as ductal carcinoma in situ, the biology of which is not well understood. Currently, the methods for classification of such lesions detected by mammography are based on the histological appearance of tissue samples, and the ability to determine their lethal potential is crude at best. The committee recognized the need for research on the progression of breast cancer to more clearly define the significance of early lesions and the need to develop biomarkers. To accomplish this goal, researchers must have access to specimens of breast tissue and fluids containing normal, precancerous and cancerous cells. The IOM committee recommended that the National Cancer Institute (NCI) facilitate expansion of and access to breast tissue specimen banks.
FDA approval and insurance coverage of new technologies used for screening should be based on a more systematic approach involving clinical trials that are coordinated and designed with support and input from relevant federal agencies and breast-cancer advocacy organizations. Private insurers also should do their part by covering the costs of screening tests for women who participate in clinical trials but who are not eligible for Medicare or Medicaid.
The final recommendation of the report urges NCI to sponsor further study of the benefits of screening mammography among women over the age of 70, which has been difficult to assess because of a lack of data from randomized clinical trials. But as the age distribution of the US population continues to shift toward older ages, the question of whether these women benefit from screening mammography will become increasingly important.
Many new technologies are in development now and promising research in basic biology is under way, but much remains to be done. The IOM report draws attention to the efforts that can improve our ability to detect breast cancer at an early stage.
The NCI and the American College of Radiology Imaging Network (ACRIN)? announced on September 4, 2001, the launching of the first large, multicenter study to compare digital mammography to standard mammography for the detection of breast cancer.
The Digital Mammographic Imaging Screening Trial (DMIST), involving 49,500 women in the United States and Canada, will compare digital mammography to standard film mammography to determine how this new technique compares to the traditional method of screening for breast cancer.
Daniel Sullivan, MD, director of the NCI Biomedical Imaging Program that sponsors and coordinates the trial for the NCI, says that “digital mammography has the potential to provide better detection of early breast cancer, but a large study is needed to really determine whether digital mammography is better than conventional mammography, and if it is better, how large the difference is.”
“Standard mammography has been the most studied screening technology over the past 40 years,” says the study’s principal investigator, Etta D. Pisano, MD, department of radiology, University of North Carolina, Chapel Hill. “What we have here is a well-proven technology, film mammography, and one that is in its infancy, not as well studied yet, digital mammography. The difference between digital and film mammography may not be large, so a large study is needed to compare the two techniques when used in screening women without symptoms.”
Digital mammography may be more effective for early cancer detection in women with dense breasts because it has improved contrast resolution. Previous studies suggest that digital mammography may result in fewer women called back for work-up of suspicious breast lesions.
Secondary aims of the study address the impact of false positives on health-related quality of life and the cost-effectiveness of digital mammography.
All images collected in this trial will be archived centrally in an online database that will be an important resource for future developers of computer-aided diagnosis (CAD) and image processing software.
A total of 19 institutions in the United States and Canada will take part in the study that will enroll the 49,500 volunteers over the next 18 months beginning on? October 15, 2001. Women will be entered into the study only at the time of their regular screening mammogram. Each woman will then be followed for several years after receiving both digital and conventional mammograms. The total cost of the digital mammography trial will be $26.3 million.
New Screening Modalities
In addition to evaluating scientific evidence on the new technologies, the IOM committee examined the process where newer screening technologies emerge from testing and enter routine clinical usage. Instruments first used in breast cancer diagnosis are not necessarily useful for screening. In evaluating a new technology’s appropriateness for screening, the FDA and the Centers for Medicare and Medicaid Services (CMS) [formerly the Health Care Financing Administration] were encouraged to base approval and coverage decisions on results of clinical trials that prove screening effectiveness, the committee said. In the ACRIN DMIST trial, four vendors have developed digital mammography systems that will be tested. The FDA currently has approved only the GE system for clinical use.
Access To Cancer Screening
Greater public access to current technologies is needed, particularly for women who lack health insurance, the report urges. Congress should expand the Centers for Disease Control and Prevention breast-cancer screening program to reach more women-from the current 15% to 70%-and state legislatures should provide Medicaid funds for treatment of women with breast cancer identified through this screening program. In addition, the CMS and a panel of independent experts should analyze the current Medicare and Medicaid reimbursement rates for mammography and comparable radiologic techniques to determine whether the cost is adequately covered. Federal agencies and professional organizations should evaluate the current and future numbers of breast imaging specialists and take measures to ensure an adequate supply of these experts.
Michael W. Vannier, MD, is head, Department of Radiology, University of Iowa College of Medicine, Iowa City, and a member of the Institute of Medicine Committee on Technology for the Early Detection of Breast Cancer.