Mammography Combined with Ultrasound
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: Combining ultrasound with mammography in high risk women improves sensitivity, but also increases false positives.
Source: Berg WA, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008;299:2151-2163.
Berg and colleagues from 21 centers in the U.S. report the results of a prospective, multicenter, randomized trial designed to validate the performance of screening ultrasound in conjunction with mammography in women with dense breasts and at high risk for breast cancer.1 The study is known as ACRIN, the American College of Radiology Imaging Network 6666 trial. Of the 2725 eligible women who ranged in age from 25 to 91, the average age was 55.1. Each patient underwent mammography and ultrasound in a randomized sequence. Forty cases of cancer were diagnosed, 12 on ultrasound alone, 12 on mammography alone, 8 suspicious with both techniques, and 8 with negative exams. Adding ultrasound yielded an additional 4.2 cancers per 1000 high-risk women. The false positive rate for mammography alone was 4.4%, for ultrasound alone, 8.1%, and for combined mammography plus ultrasound 10.4%. Thus adding ultrasound to mammography screening in high risk women with dense breasts improved the sensitivity of screening, but increased the rate of false positive examinations. Breast cancer mortality was not an endpoint in this trial, but the fact that the cancers detected by ultrasound are usually asymptomatic, node-negative, and not detected by mammography should yield a reduction in mortality.
Commentary
The impact of screening mammography has been established by multiple randomized trials: about a 22% reduction in breast cancer mortality in women 50 years old and older, and 15% in women between ages 40 and 49. But at the same time it is recognized that it is difficult for mammography to detect noncalcified masses, especially in dense breasts. This sensitivity problem has been improved by digital mammography, but not eliminated.
Ultrasound screening can detect cancers not seen on mammography and its performance is not affected by dense breast tissue. Adding ultrasound to a screening program seems like a no-brainer, but its impact on mortality reduction has not been measured in a large trial. In the single center studies of screening ultrasound that have been published, cancers have been found only by ultrasound, and most are small, early stage tumors. During the conduct of the above trial, an Italian multicenter study reported that 29 cancers were found by ultrasound in 6449 women with dense breasts and negative mammograms.2 Nevertheless, a majority of facilities do not offer screening ultrasound because of a lack of qualified personnel and standardized protocols.
The problem with all screening methods is a substantial rate of false positives. In this study, 91.4% of suspicious ultrasound findings were benign. The positive predictive value for ultrasound was only 8.6%, but the value for mammography was only 14.7%. Remember that ultrasound tends to find earlier tumors. The crucial question is how many false positives are worth the gain in additional cancer diagnoses. In this study, the gain was an additional 29% (the number of cancers detected only by ultrasound). In women with elevated risks, this seems worthwhile. Women at high risk probably have a greater fear of diagnosing breast cancer late than of a false positive.
Combining MRI with mammography yields a very high sensitivity, and this is now recommended for women at very high risk for breast cancer. MRI, of course, is the most sensitive technique, but it is very expensive, requires the intravenous injection of contrast, and isn't always tolerated by patients. Ultrasound has the advantage of being less expensive, easily tolerated, and widely available. Thus the combination of ultrasound and mammography seems best for women of intermediate risk. Ultrasound has a disadvantage of not detecting ductal carcinoma in situ, which is detected by mammography and MRI.
The final protocol for the best screening use of the three modalities—mammography, ultrasound, and MRI, will also require consideration of cost. The total cost is a complex summary of the technology, the time consumed, the increase in patient anxiety and discomfort, and the expense of additional testing because of false positives. Nevertheless, the evidence now seems sufficient to individualize decision-making and to recommend more than the single technique of mammography for high risk patients (defined as a combination of factors that produces a 3-fold increase in risk), especially in women with dense breasts. Thus far, over 90% of cancers detected only on ultrasound have been in women with dense breasts. Ultimately the best screening method, MRI, may become cost effective. How much cost is justified for a life-saving method?
References
- Berg WA, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008;299:2151-2163.
- Corsetti V, et al. Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts. Radiol Med. 2006;111:440-448.
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