Many Don’t Want to Know Genetic Risk of Cancer
Given a chance to learn if they carried a gene that raised their risk of developing breast, ovarian or prostate cancer, surprisingly few of the 279 women and men in a new study--only 43%--chose to take such a look at the future.
That was a central finding of the largest study yet of how people react when offered a blood test for the so-called breast cancer gene, BRCA1, which boosts the likelihood of developing the disease to 87%, about eight times higher than that of women generally. The gene also confers a 40% to 60% lifetime risk of ovarian cancer and about a 10% risk of prostate cancer in men.
Among the study subjects, who belonged to families with pronounced histories of breast and ovarian cancer, a major reason for declining the BRCA1 test was fear that a positive result would jeopardize health or life insurance. Another prominent fear was that a faulty test would mistakenly register, and perhaps stigmatize, a non-carrier as positive, prompting much needless anxiety and perhaps even surgery.
The issues raised by the study spotlight an emerging dilemma that pits a newly acquired power of science, which literally means “to know,” against the foremost of medical ethics, which is to do no harm.
The study “is a very important contribution to understanding . . . what possible choices people will make when they face the actual experience,” said Dr. Francis Collins, director of the National Center for Human Genome Research at the National Institutes of Health.
“Being concerned about insurability and discrimination is very unsettling to people and may dissuade them from seeking testing,” said Dr. Henry Lynch, a cancer specialist at Creighton University in Omaha and coauthor of the study. It appears today in the Journal of the American Medical Assn.
At the same time, the study uncovered real psychological and medical benefits of being tested. People who worried that they might have the gene and suddenly learned that they did not--instead, they had the same cancer risk as women generally--became less depressed.
Testing negative for the gene also has the potential to spare women unnecessary surgery, the study showed. Before the test was available, women whose family history placed them at high risk of cancer sometimes had their breasts or ovaries surgically removed, the only known way to help prevent the diseases from developing.
Indeed, 15 women who had previously undergone either type of surgery learned from the test that they did not harbor the BRCA1 gene after all.
“The net result of [wider testing] is that we will be able to do fewer surgeries and still prevent the same number of cancers,” said study coauthor Dr. Steven Narod, a medical geneticist at Women’s College Hospital in Toronto.
And contrary to the researchers’ expectations, subjects who tested positive for BRCA1 did not appear to be particularly depressed by the news when interviewed by phone a month after the results were divulged.
“If we prepare people adequately, educationwise, and inform them of the test results with careful genetic counseling, we can perhaps ward off undue emotional reactions,” said Lynch, who for 35 years has pioneered the study of families afflicted by hereditary cancers.
Since its discovery in 1994, BRCA1 has been the focus of intense research and some controversy. Generally, says Dr. Barbara Weber of the University of Pennsylvania School of Medicine, the mutated gene is responsible for 50% of inherited breast cancer cases, or up to 5% of all breast cancers. The American Cancer Society says that about 182,000 women develop breast cancer annually in the U.S.
Biotechnology firms have rushed to develop the BRCA1 test and others like it for possible use outside of a research setting. But critics, like the watchdog Council for Responsible Genetics, say hasty commercialization could lead to an epidemic of insurance discrimination.
A spokesman for the Health Insurance Assn. of America, however, said it is unfair for consumers to withhold knowledge, even predictive genetic information, of a problem from an insurer. “The insurance industry needs to be on an equal footing with an applicant,” he said.
Although the new study offers the strongest documentation yet of reactions to the BRCA1 test, researchers say it may underestimate the fears that people have about the test’s consequences.
That is because the screening was done in the context of an ongoing research project, where the test was free and teams of health-care workers systematically counseled and treated whole families.
In contrast, out in the hurly-burly of managed care, people might feel even less secure about undertaking the test and divulging details of what Lynch called their “lifetime cancer destiny.”
For now, Lynch said that only women in families with a very strong history of breast cancer should be tested for BRCA1 or BRCA2, a closely related cancer gene. Women who test positive are encouraged to have a physical breast exam twice a year and mammography once a year beginning at age 25.
In the new study, 17% of women who carry the BRCA1 gene indicated that they would opt for a preventive double mastectomy. Annual ultrasound ovarian cancer screening is also recommended; as a preventive measure, some women consent to have their ovaries surgically removed at age 35.
“I don’t think this sort of testing is ready yet to be done outside a research environment,” Collins said. “We don’t know enough about the consequences and we don’t know for sure if the interventions work.”
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NEXT STEP
* Being tested for a gene such as BRCA1, which researchers say is responsible for about 50% of inherited breast cancer cases, is so fraught with dilemmas that the American Society of Clinical Oncology drew up guidelines this year to steer doctors and patients through the process. Among things a person considering a test should know:
* Implications of a positive or negative result.
* Possibility that the test result will be uncertain.
* Other options for evaluating cancer risk, such as family history.
* Risk of passing the mutated gene to one’s children.
* Fees involved in testing and counseling.
* Risk of psychological distress.
* Risk of insurance or employer discrimination.
* Confidentiality of result.
* Strengths and limitations of medical options and surveillance after testing.
