Uncertain gene test result can feed cancer worries

By Amy Norton

NEW YORK (Reuters Health) - While genetic testing for breast cancer risk can offer some women valuable information, those who get an inconclusive result can end up with lingering anxiety, a new study suggests.

Mutations in the genes BRCA1 and BRCA2 are responsible for about 5 percent to 10 percent of breast cancers, and women with a strong family history of breast cancer can get BRCA testing to see whether they carry a mutation that raises their risk of the disease.

However, the results of those tests are often not black-and-white.

Some women come away with a "true negative" -- meaning they do not carry specific BRCA mutations that have been found in a family member with breast cancer, making it unlikely they have an inherited susceptibility to the disease.

In many cases, though, a woman will have a strong family history of breast cancer, but the specific mutations that run in the family are unknown.

She may test negative for generally known BRCA mutations. The possibility of developing hereditary breast cancer cannot be ruled out because there may be yet-undiscovered BRCA mutations linked to the disease.

The new study, reported in the journal Genetics in Medicine, suggests that for some women, such inconclusive test results can be as distressing as a positive result.

The findings are based on assessments of the long-term psychological adjustment of 215 women who had undergone BRCA testing. Of the group,

37 tested positive for a gene mutation, 31 received a true negative, and 147 got an inconclusive result.

Dr. Sandra van Dijk and colleagues at Leiden University Medical Center in the Netherlands found that, several years after being tested, women in the true-negative group showed the best adjustment.

Not surprisingly, they had the least worry over their cancer risk and the easiest time coming to terms with their test result.

In contrast, women with an inconclusive result were typically as concerned about cancer as their counterparts with a positive test result and they were less able than the true-negative group to come to terms with their test findings.

The findings, according to the researchers, underscore the importance of genetic counseling before and after BRCA testing to ensure that women have realistic expectations of the test and fully understand the results.

"It seems that many women expect certainty and do not realize that it is difficult to rule out a genetic explanation for multiple cases of breast cancer among family members," van Dijk told Reuters Health.

Because of this, she explained, genetic testing may not provide them with the "relief" they'd hoped for.

"Adjustment of expectations seems to be important in coming to terms with the result," van Dijk said, "and should be addressed by genetic counselors prior to DNA testing."

It's not clear how to best help women with inconclusive results cope with their long-term uncertainty. Studies are still needed to answer that question, van Dijk and her colleagues add.

SOURCE: Genetics in Medicine, October 2008.