Ultrasound spots mammo misses, but at high cost

Screening ultrasound paired with mammography improved breast cancer detection in high-risk women, but the combination also caused a spike in the number of false positives, according to an update to the American College of Radiology Imaging Network 6666 trial. These results may render ultrasound less attractive than MRI in this patient population.

"Supplemental screening ultrasound has the potential of depicting small, node-negative breast cancers not seen on mammography," wrote Dr. Wendie Berg, Ph.D., et al in the Journal of the American Medical Association (2008;299[18]:2151-2163).

Berg's group presented these findings at the 2007 RSNA meeting. ACRIN 6666 was funded by the Avon Foundation and the National Cancer Institute.

In the ongoing trial, 2725 women, 53% of whom had a personal history of breast cancer, were scanned at 21 sites. Two-view mammograms were done on either screen-film or digital units. Ultrasound scans were performed in the transverse and sagittal planes with a 12-MHz transducer.

In ultrasound's favor, 40 out of 2725 women were diagnosed with cancers, eight of which were found with mammography and ultrasound while a dozen were deemed suspicious on ultrasound alone. The diagnostic yield for the combined modalities was 11.8 per 1000. Diagnostic accuracy came in at 91% for mammography plus ultrasound versus 78% for mammography alone. Of the 12 sonographically detected cancers, 92% were invasive.

However, for combined imaging, the false-positive rate jumped to 10.4% (versus 4.4% for mammography alone), with the majority of cases composed of complicated cysts. The median ultrasound exam time came in at 19 minutes, and current Medicare reimbursement rates do not cover the costs of performing and interpreting the exams.

In a JAMA editorial, Dr. Christiane Kuhl, MRI section chief at the University of Bonn in Germany, pointed out that the false-positive ultrasound results may be more benign than false-positive mammographic results, as the latter require additional study with invasive biopsy techniques. Still, Kuhl said that ultrasound's drawbacks may render MRI the better bet (JAMA 2008;299:18:2203-2205).

"With modern high-frequency probes, screening both entire breasts is a time-consuming endeavor," she said. "The actual costs will be substantially higher than what is reflected by the respective billing codes. Due to the amount of physician time screening ultrasound requires, it may be the most expensive of all breast imaging modalities."

Berg countered that the overall price of MR studies tipped the balance in favor of ultrasound. While staffing shortages may not make it possible for physicians to learn breast sonography, other options are available.

"Training specialized technologists in breast ultrasound is feasible, and the materials we have developed for ACRIN 6666 can help with this," Berg said. "Methods of automated breast ultrasound may solve many of these issues, but such technology requires further validation at this time."

Based on their individual risk factors, many women can be stratified to undergo ultrasound.

"There is a large group of women at increased risk for breast cancer for whom MRI may or may not be warranted, including women with a personal history of breast cancer, prior atypical biopsy, dense breast tissue, or intermediate family history," Berg said. "It is this latter group for whom ultrasound can be considered."

Last year, breast MR received a boost from the American Cancer Society when it recommended that women who meet certain high-risk criteria undergo regular screening with breast MR. Berg said she hoped that ACRIN 6666 will raise breast ultrasound's profile in a similar way.

"These results provide important validation for screening ultrasound under well-controlled circumstances," Berg said.ACRIN 6666 participants concluded a third round of sonographic screening in March 2008. Many of the subjects also will undergo breast MR. Follow-up results should be available in 2009.

"We are anxiously awaiting the results of the second- and third-year screening ultrasound examinations . . . to better understand if this exam has benefit on an annual basis, and whether or not false positives are reduced in subsequent years," Berg said.