Physicians Must Weigh Risks and Benefits of Genetic Testing

SAN FRANCISCO--Whether to administer genetic testing to a patient is a complex issue, Patrice Watson, PhD, of Creighton University School of Medicine, Omaha, said at the American Cancer Society Second National Conference on Cancer Genetics.

"Certainly these tests have costs and benefits. They’re expensive, first of all, and they can be inconclusive. And with these tests, patients receive knowledge of their transmission risk, which can lead to discrimination and anxiety," she said.

That is why Dr. Watson believes that clinicians should consider not only the potential health impact of the test--ie, that it will lead to increased screening and prevention--but also the potential emotional and economic impact.

"We also have to consider the test sensitivity in deciding whether the patient should have it. Is it really worth giving?" she said. When considering the BRCA1 and 2 tests for hereditary breast and ovarian cancer, for example, the clinician needs to take accuracy into account.

Researchers estimate that BRCA testing has an 80% sensitivity and a 99% specificity. "And the researchers are making an optimistic estimate of sensitivity," Dr. Watson said. "In reality, the tests may miss many people who have the carrier gene. We really don’t know the true sensitivity and specificity of this test, and the results often depend on the nature of the mutation search--and the type of mutation found."

Regarding breast and ovarian cancer, she said, the probability of a positive BRCA1 or 2 gene mutation test are quite low even in those with a family history of breast cancer. "It’s only in the small family subgroups with a striking family history that there is a high proportion of positive results," she said. Because the likelihood of a positive test result is so small, the value of this test is reduced.

Even less is known about the hereditary nonpolyposis colorectal cancer (HNPCC) test. Of those who take the test, about 50% get a positive result, she said. So the sensitivity of the HNPCC test is much less than that of tests for BRCA1 and BRCA2. "At the same time, the probability of a positive result in someone with a striking family history is probably high," she said.

For both tests, therefore, the best candidates are those with a striking family history and personal history of disease, Dr. Watson concluded. Because there is such a low probability of finding the gene, clinicians should realize that the vast majority of those with a family history of cancer will test negative.

That’s why taking a family history--and truly deducing whether or not the family history is striking--is such an important issue in genetic testing. "With such a history, you can give family members the greatest amount of information and tell them how this disease might affect them," she said.