Ordinary mammograms are not accurate as desired.   Computer-Aided Detection (CAD) software designed to help radiologists read mammograms makes the screening procedure even worse.   Mammography coupled with CAD results in much more false positive diagnoses of breast cancer compared to ordinary mammography, a new study shows.

Use of CAD did not improve the detection of breast cancer and could only increase the rate of false positives that lead to unnecessary medical treatments such as biopsies and emotional stress, found investigators at the University of California Davis Health System, Sacramento, Calif., and colleagues in the Breast Cancer Surveillance Consortium.

Findings appear in the April 5, 2007 issue of the "New England Journal of Medicine" and the study was funded by NCI, the Agency for Healthcare Research and Quality, and the American Cancer Society.

Women who received screening mammograms at centers using CAD were more likely to be told their mammogram was abnormal and asked to undergo a biopsy to confirm if there is breast cancer, the study revealed.

CAD software was designed to analyze the mammogram and marks suspicious areas for physicians to review and determine which spots may lead to serious cancer. It was approved by the U.S. Food and Drug Administration in 1998 and incorporated into mammography imaging practices while the accuracy of interpretation of mammograms is not clear.

"Within three years of FDA approval, 10 percent of the mammography facilities in the country were using CAD," said lead researcher Joshua J. Fenton, M.D., UC Davis Health System.   "There had been no large-scale community-based review of CAD efficacy despite the rapid adoption of this technology so we did this study to see if CAD was proving to be beneficial."

"This study points out the need for the use of other techniques to find cancer at its earliest stages.   NCI is incorporating techniques for imaging at the molecular level into many of its studies and is also conducting studies to improve the use of CAD and conventional mammography," said John E. Niederhuber, M.D., NCI Director.

"In the end, technology facilitates screening. Ultimately, treatment requires radiologists working with the examining physician and the responsible surgeon to put everything together. We worry about false positives, but we certainly don’t want to miss any cancers, either."

In the study, investigators looked at the use of screening mammography in 222,135 women at 43 facilities in Colorado, New Hampshire, and Washington states, who had 429,345 mammograms from 1998 through 2002.    Among the subjects, 2,351 women received a diagnosis of breast cancer within one year after screening and also received a mammogram that did or did not use CAD.

Computer-aided detection was used in 16 percent of the study sites or seven facilities during the study period.   The facilities using CAD recalled 32 percent more women for further tests and 20 percent more women had a breast biopsy.

However, use of the software had no clear positive impact on the early detection of breast cancer.   If there is anything different, the software may promote the detection of the least dangerous breast cancers, such as localized, in situ breast cancers, the study suggests.   But the effect of accurate detection of in situ cancers on breast cancer mortality remains unknown.

For every mark resulting from CAD that truly suggests a real cancer, a radiologist had to consider about 2,000 additional false-positive marks, making it almost impossible to distinguish between real cancers and those that are not cancer.

For every additional woman to be diagnosed with real breast cancer on the basis of CAD, 156 women would be falsely recalled for more tests and 14 had unnecessary biopsies to exclude cancer, according to the authors.

"It’s unfortunate that the use of the software has proliferated so widely before we are certain of its benefits," said Fenton.   "We need studies to determine if the benefits of the software outweigh its harms and costs.   There is also the potential for new studies to improve the performance of CAD software."

Computer-Aided Interpretation of Mammograms: Questions and Answers from cancer.gov


Key Points

• In 1998, the FDA first approved a device that helps radiologists display and interpret mammograms. Like a scanner, the device converts a film mammogram into a digital file that can be analyzed by computer software. CAD software analyzes the mammogram image and marks suspicious areas for the radiologist to review in association with their own reading. (Question 1)
• The study reported in the April 5, 2007, issue of the New England Journal of Medicine showed that computer-aided interpretation of mammograms was less accurate than interpretation without a computer’s help and that computer software designed to improve mammogram interpretation may actually make it worse. (Question 2)
• CAD can be applied to either film or digital mammograms. Before CAD is applied to film mammograms, they are converted to a digital image. (Question 4)

In 1998, the U.S. Food and Drug Administration first approved a device that helps radiologists display and interpret mammograms. Like a scanner, the device converts a film mammogram into a digital file that can be analyzed by computer software and displayed as a copy on a TV or computer screen. Called computer-aided detection (CAD), the software analyzes the digital representation of the mammogram image and marks suspicious areas on the screen image for the radiologist to review in association with their own reading of the original film. Preliminary studies suggested that the device helped in detection of cancer. Medicare and many insurers now reimburse for the application of CAD. The software has since spread into practice, and it is estimated that about 30 percent of mammograms are now interpreted using one of these devices.

The study reported in the April 5, 2007, issue of the New England Journal of Medicine* showed that computer-aided interpretation of mammograms was less accurate than interpretation without a computer’s help and that computer software designed to improve mammogram interpretation may actually make it worse. With CAD, women were more likely to be told their mammogram was abnormal and to have undergone additional evaluation or biopsy to rule out breast cancer.

With the software, 32 percent more women were recalled for additional tests and 20 percent more women had a breast biopsy even though most didn’t ultimately have breast cancer. Use of the software had no clear impact on the early detection of breast cancer. If anything, the software may promote the detection of the least dangerous breast cancers, or in situ breast cancer. These sometimes grow so slowly that they would never come to clinical attention in the absence of screening. At this time, scientists are uncertain whether detection of these cancers by screening reduces a woman’s chance of dying from breast cancer.
The software had no significant impact on the detection of more dangerous invasive breast cancers.

Both digital and film mammography use X-rays to produce an image of the breast. In film mammography, which has been used for over 35 years, the image is created directly on a film. Once a film mammogram is obtained, it cannot be significantly altered; if the film is underexposed, the contrast, which is the difference between the lightest and darkest areas on a display screen, is lost and cannot be regained.
Digital mammography takes an electronic image of the breast and stores it directly in a computer. Digital mammography allows improvement in image storage and transmission because images can be stored and sent electronically.
With CAD, the film mammogram is converted to a digital image. But this converted image is like a digital copy of a photograph, whereas with digital mammography, the ‘picture’ of the breast is directly recorded as a digital image and can be magnified and manipulated like people magnify and manipulate a digital photograph. CAD reviews patterns of the digital image to alert the radiologist to spots that could be cancer, but how it works with digital mammograms may be different than how it works with converted images of regular mammograms. This difference needs careful study and has not yet been resolved.

With CAD, the computer analyzes the digital image and marks suspicious areas on a copy of the mammogram shown on a screen. Radiologists must compare the marked image and the film mammogram to find cancers they might have missed with the naked eye. They cannot manipulate the image on the screen like radiologists can manipulate a digital mammogram. Radiologists are taught to use CAD, but there is no additional certification process for them to use this approach.

Women should be informed about the strengths and weaknesses of what is known about CAD, but this study does not address whether risks outweigh the benefits of its use. That kind of study could provide better guidance about what women should do.
In medicine, there is a long tradition that physicians should "first, do no harm." This study raises the question of whether harm is being done with CAD because of increased recall rates and more biopsies. On the other hand, it remains uncertain whether CAD benefits women by uncovering serious breast cancers.

NCI recommends that:

• Women in their 40s should be screened every one to two years with mammography
• Women aged 50 and older should be screened every one to two years
• Women who are at higher than average risk of breast cancer should seek expert medical advice about whether they should begin screening before age 40 and the frequency of screening.

Women can ask their doctors or contact local hospitals or imaging centers to find out if CAD is routinely used. Mammogram reports will typically contain a statement of whether or not CAD was used to assist in image interpretation. Film mammography is still much more common than digital mammography.

Women should have their next mammogram when they are scheduled for it. At the individual level, the overall accuracy of mammography using each of these techniques is more similar than different. It would be better to have a film mammogram when a woman is supposed to have her next mammogram than for her to delay her screening on the basis of her preference for receiving screening with or without CAD or digital mammography.

CAD only impacts the interpretation of the images after they are obtained. From a woman’s perspective, the positioning and compression of the breast are identical.

In addition to mammography, ultrasound and magnetic resonance imaging (MRI) are both sometimes used to screen for breast cancer in women at very high risk of the disease. A large, NCI-sponsored study comparing ultrasound vs. mammography in high- risk women is currently in progress.
There are no multi-center clinical trials that have proven the superiority of MRI or ultrasound compared to mammography as a means of screening for breast cancer among the general population of women over age 40.

The U.S. FDA reports that there are about 33.5 million mammography procedures performed per year in the United States. Data from 2000-2002 show that about 70 percent of all mammograms that are performed annually are for screening purposes (to detect cancer in women with no symptoms as opposed to following cancer once it has been diagnosed). This translates to about 23.5 million screening procedures every year.

Reimbursement by Medicare in 2005 for film-screen mammograms was $85.65 and for digital screening mammography (for women with two breasts, as opposed to those who have undergone mastectomy) was $135.29. Actual cost for mammograms will vary by region and the form of reimbursement. Medicare provides an additional $20 for reimbursement if CAD is used to supplement interpretation of screening mammography.

Researchers need to conduct larger studies to clarify whether and how CAD software improves cancer detection. Studies are also needed of whether any possible benefits of the software outweigh its harms and costs. There is also the potential for research to improve the accuracy of the CAD software.

Screening MRI has never been tested in women who are at average-risk for breast cancer, so it is not known whether it is effective and safe. Women should continue to get regular screening mammograms. On March 28, 2007, the American Cancer Society issued guidelines for the use of MRIs for breast cancer screening among women at high-risk for breast cancer. Those guidelines can be found at http://caonline.amcancersoc.org/cgi/content/full/57/2/75.

There are several manufacturers of FDA-approved CAD devices in the United States, including R2 Technology, Inc., Santa Clara, Calif. (ImageChecker), iCAD, Inc., Nashua, NH (SecondLook), and Kodak, Inc. The R2 Technology product was the first to receive FDA approval and manufactured the devices used by facilities in this study. In one comparative study, the R2 Technology and iCAD products had similar effects on radiologists’ interpretation of mammograms.

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