The "coming of age" of nonmammographic screening for breast cancer.

THE STUDY BY BERG AND COLLEAUGES 1 PUBLISHED IN this issue of JAMA addresses important clinical questions: What is the additional cancer diagnosis yield of screening ultrasound in women at increased risk of breast cancer, and what are the “costs” of such strategies in terms of false-positive diagnoses. The design of this American College of Radiology Imaging Network (ACRIN) trial, from the multi-institutional setting to source documentation and independent data analysis, is excellent from every aspect. This study and several other previously published trials demonstrate how important it is to have institutions like ACRIN sponsor and help organize prospective clinical trials that follow good clinical practice in the world of diagnostic imaging, which, unlike clinical research in the therapeutic sector, has to proceed without the financial support and scientific infrastructure usually provided by the pharmaceutical and medical device industries. The results of this study are impressive. Ultrasound was associated with a 55% increase in diagnosing breast cancer compared with mammography alone: a 7.6 per 1000 to 11.8 per 1000. The sensitivity with which breast cancer was detected was 77.5% (32 of 41) for the combined use of ultrasound and mammography vs 49% (20 of 41) for mammography alone. Given that mammography is the standard of care, one could argue that a main finding of this study is the apparently limited sensitivity of screening mammography. However, this finding is in keeping with recent results of several mammographic screening studies. Depending on the composition of the screening cohort, the sensitivity can be as low as 25% for BRCA1 mutation carriers, but even in women at average risk, for instance in almost 50 000 women who participated in theDigitalMammographic ImagingScreening trial, theoverall sensitivity of screening mammography was only 55%. It is well established that mammography and ultrasound are complementary for diagnosing breast cancer. Ultrasound performs best in cases for which mammography performs weakest, ie, in breast areas with of dense fibroglandular tissue. Yet, breast ultrasound is seldom used for screening in the United States, and to date, none of the worldwide screening programs offers ultrasound. Reservations against the use of ultrasound include costs, frequency of falsepositive findings, and lack of evidence from randomized trials on mortality end points. The results from this study by Berg and colleagues confirm that the positive predictive value of screening ultrasound is indeed low. Of 233 women for whom biopsy was recommended based on a suspicious ultrasound finding, only 20 (8.6%) were diagnosed with breast cancer. Stated otherwise, 91.4% of all suspicious ultrasound findings identified by expert breast radiologists were due to benign changes. Although this seems to be a key argument against the use of breast ultrasound, one should consider that mammography, the accepted standard of care for screening, had a positive predictive value of 14.7% (20 of 136) in the same cohort. In the cohort of 2712 women, the number of falsepositive diagnoses increased from 116 (for mammography alone) to 275 (for the combined use of mammography and ultrasound). This might be considered far too many. But this has to be weighted against the benefit of the additional cancer diagnosis yield of ultrasound. Twelve cancers, ie, 29% of the total 41 cancers, were only detected by ultrasound. Whether this is sufficient to justify the many false-positive ultrasound diagnoses is something every individual woman may have to decide for herself. Of note, comparing only numbers of false-positive diagnoses may not be fair because a suspicious finding made by mammography usually requires stereotactic, mostly vacuumassisted biopsy, an expensive and time-consuming procedure. In comparison, a positive ultrasound finding can be investigated by ultrasound-guided core biopsy (or even fineneedle aspiration), a simple, fast, and inexpensive procedure that often may be performed immediately. Accordingly, the average false-positive ultrasound may not have the same implications as the average false-positive mammographic diagnosis. This statement should not downplay the problem. Falsepositive diagnoses should be avoided not only because they add to the overall costs of a screening program but also because they may stimulate unnecessary anxieties. However, a recent study on the psychological impact of false-positive screening diagnoses concluded that “women who are re-