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Cancer-Risk Test Not Fail-Safe

Posted on: Wednesday, 22 March 2006, 21:00 CST

By Andy Pollack New York Times News Service

The widely used genetic test for breast cancer risk can miss mutations that help cause the disease, according to a new study, a finding that is likely to increase the pressure to develop more thorough testing methods.

The test, which looks for mutations in genes called BRCA1 and BRCA2, missed them in about 12 percent of breast cancer patients from families with multiple cases of breast or ovarian cancer, according to the study's authors at the University of Washington.

Experts cautioned that the chances of such false negative results were much smaller for women who were not from such high-risk families, so that most women who tested negative had little cause for concern.

In addition, experts said that even Ashkenazi Jews, who have a relatively high incidence of mutations, tend to have specific types that are not likely to be missed by the test. Also, if a woman is tested for the same specific mutation her mother has, the test is not likely to miss it if it is there.

Still, experts said women in families with multiple cases of breast and ovarian cancer should take precautions as if they had a mutation, even if none was found.

"Everyone who has a strong family history and is negative should be considering how negative that result really was," said Dr. Judy E. Garber, director of the cancer risk and prevention program at the Dana-Farber Cancer Institute in Boston.

The new study, being published in The Journal of the American Medical Association, is likely to increase the pressure on Myriad Genetics, which offers the test.

The company, based in Salt Lake City, has long been the focus of controversy because its patents give it a monopoly on the test, for which it charges as much as $3,000. Some geneticists say the monopoly has slowed development of better testing.

Gregory Critchfield, head of the laboratory unit at Myriad, told Bloomberg News that his company plans to release an expanded test later this year that could pick up some additional mutations.

"A fuller testing process would include more than one technology, and competition would enable that to develop," Mary-Claire King, a professor of medicine and genome sciences at the University of Washington and senior author of the paper, said in an interview.

King said a technique that could detect many of the missed mutations was already available in Europe but not in the United States, except in research projects.

Dr. Gregory C. Critchfield, president of the genetic testing division of Myriad Genetics, denied that the company's monopoly had impeded progress. The company hoped to have a more thorough test available by the end of the year, Critchfield said.

Five percent to 10 percent of breast cancers in white women in the United States stem from inherited mutations in the BRCA genes. Tens of thousands of women a year get the test, Myriad Genetics said.

Women with a mutation have a much higher risk of getting breast or ovarian cancer than the general population. Such women usually undergo more frequent screening to try to catch the cancer early, when it is more treatable. Some women opt to have their ovaries or breasts removed to prevent the disease.

Experts have long known that Myriad Genetics's test misses certain types of mutations it is not designed to detect. But the new study is believed to be the most extensive effort to quantify how often that occurs.

"We've known parts of the story but she's pulled it together very well," Lynn Hartmann, a professor of oncology at the Mayo Clinic, said of King's study.

King and her co-authors studied 300 women who had negative test results and who came from families with four or more cases of breast or ovarian cancer. The authors used various testing techniques beyond the one used by Myriad Genetics and found mutations in 35 of the women. None of the 30 Jewish women in King's study were found to have mutations undetected by Myriad Genetics.

Critchfield of Myriad Genetics said only 6 percent of the women who got the test came from such high-risk families. If the test is wrong for 12 percent of them, he said, then the rate of false negatives for all women tested is less than 1 percent.

The Myriad Genetics test looks for mistakes in the sequence of genetic letters in parts of the gene that contain the recipe for proteins. But it can miss errors in other parts of the gene, or deletions and duplications of chunks of DNA.

Source: Deseret News (Salt Lake City)

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