Genetic Tests for Cancer Not Perfect

Cancer :: Genetic Tests for Cancer Not Perfect

For women with genetic mutations that increase their risk of breast and ovarian cancer, genetic testing has been a godsend. The tests allow them to learn if they carry mutations in the BRCA 1 and BRCA 2 genes, and if they do, to decide what action to take, such as stepping up screening or undergoing a preventive mastectomy.

But the tests aren't perfect, a new study found. About 12 percent of 300 breast-cancer patients from high-risk families carried mutations that were previously undetected with standard genetic tests, according to a study in the March 22/29 issue of the Journal of the American Medical Association.

Between 2002 and 2005, a research team from the University of Washington and other facilities evaluated 300 breast-cancer patients who were the first member of a family to come under study due to the diagnosis. The researchers used multiple, different screening tests to identify mutations not only in the BRCA 1 and BRCA 2 genes, but also other inherited mutations in other genes that can predict breast cancer, such as CHEK2, TP53 and PTEN.

The scientists found that 17 percent of the patients carried mutations that were previously undetected, and that 12 percent of them had "rearrangements" in the BRCA1 or BRCA2 genes that the standard tests failed to pick up. The failure of the standard tests was more frequent among patients diagnosed when they were under age 40 than those diagnosed at older ages.

The researchers used a diagnostic technique called multiplex ligation-dependent probe amplification, or MLPA, a molecular way to detect genetic variations. The technique is currently not available in the United States, according to the study authors.

They noted that more effective methods for identifying the mutations should be made available.

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, called the findings significant. "This study increases the importance of having a consult with a competent genetic counselor."

The standard commercial test for BRCA 1 and 2 mutations is probably more likely to work for women of Ashkenazi Jewish descent, who've been known for years to be at higher risk for the mutations, he said.

Lifetime risk of breast cancer is as high as 80 percent among women in the United States who have mutations in the BRCA1 and BRCA 2 genes. The risk of ovarian cancer is 40 percent or higher for those who carry a BRCA 1 mutation, and 20 percent or higher for those who carry the BRCA 2 mutation. Young women are at especially high risk, the researchers noted.