GAITHERSBURG, MD. -- A device intended for use in the annual breast cancer screening of women aged 30-39 years who have no family history of the disease and a negative clinical breast examination was found not effective in a unanimous vote by the Food and Drug Administration Obstetrics and Gynecology

The T-Scan 2000ED is manufactured by Mirabel Medical Systems and uses a 1-volt electrical current to collect 306 measures of impedance for each breast. Mirabel believes differences in impedance can indicate the presence of cancer; women with positive results would then be referred for mammography or ultrasound. (Women younger than 40 years old who have no family history of breast cancer are currently not recommended for mammography because of denser breast tissue and the lower incidence of breast cancer in this age group.) A positive T-Scan result is shown on the operator's monitor as a red line, and a negative result appears as a green line; no tissue imaging is produced.

A principal objection of the panel was that the sensitivity arm of the study included women aged 30-45 years, rather than just the 30-39 target age group included in the specificity arm. Moreover, both arms included clinical sites in Israel, where the population is dissimilar to that of the United States in ethnic makeup, body mass index, and possibly brassiere cup size and other factors, panel members noted.

The racial composition of both study arms also raised concerns, in that minority patients were underrepresented in comparison with the U.S. population, several panel members noted. In the specificity arm, 1.5% of the patients were of Asian descent, 2.9% were black, and 2.7% were Hispanic. In the sensitivity arm, 2.3% were Asian, 8.0% were black, and 4.6% were Hispanic.

The prospect of needlessly alarming patients with positive T-Scan results later belied by negative mammograms was raised by the panel. The FDA deduced from Mirabel's data that using a prevalence of 0.0015 in a population of 10,000 women, 530 would receive false positives. At the same time, T-Scan would identify 4 of 15 expected cancers in the group and miss roughly 11 cancers. Some panel members worried that false positives would lead to increased patient anxiety that might not be assuaged by negative mammogram testing. Specificity was calculated at 94.7.

Also of concern to some panel members was the predetermined requirement of 2 for relative probability, meaning that any woman in the target age range with a positive T-Scan finding would need to be twice as likely to have breast cancer than the average woman in the 30- to 39-year-old population. Relative probability was ultimately determined to be 3.6. However, at least one panel member regarded the threshold of 2 as inappropriate.

"I think the 2 hurdle is much too low.... It absolutely must be associated with age. A 30-year-old is incredibly different from a 39-year-old in terms of risk for breast cancer," said Donald Berry, Ph.D., chairman of biostatistics and applied mathematics at the University of Texas M.D. Anderson Cancer Center.

According to the FDKs analysis of the sensitivity trial, there were four confirmed cancers in women aged 30-39 who had negative clinical breast examination findings and negative family history of cancer. Two cases were in the United States, and two were in Israel, where one was detected by the T-Scan. An additional 11 cancers were confirmed in the 40-45 age group, of which 4 were detected by T-Scan. Thus the device detected 5 of 15 overall cancers and 1 of 4 cancers in women younger than 40, for a sensitivity rate of 25%, the FDA concluded.

"We have, at the maximum, 15 cancers and five assessments by T-Scan; this would establish a new low for the FDA in terms of level of evidence," Dr. Berry said before the 10-0 vote.

However, several gynecologists spoke in favor of approval in the public comments forum at the meeting. Dr. Steven Goldstein, professor of ob.gyn, at New York University, noted that whereas 12,000 women aged 30-39 are diagnosed with breast cancer each year, only 9,000 women total are diagnosed with cervical cancer annually. "For all the talk these days about HPV and vaccines, the cervical cancer success story is really the result of screening--the Pap smear." Moreover, "Clinical use allows maturation and further refinement of virtually all medical technology, and I'm confident the same would be true of electrical impedance, if given the chance," he added.

No panelists had concerns regarding the safety of the device.

The FDA usually follows the recommendations of its advisory panels.

BY JOHN R. BELL

Associate Editor