CANCER SPECIALISTS PONDER ETHICS OF NEW TESTS
By Sean Henahan, Access Excellence
The development of a genetic test for determining breast cancer risk highlights a number of the medical and ethical issues that are bound to become more pressing as the number of genetic tests for different cancers proliferate, reported researchers at the annual meeting of the American
Society of Clinical Oncology.
Last year researchers announced data linking mutations in
the BRCA1 gene to rare familial forms of breast and ovarian
cancer. Subsequent studies showed that the BRCA1 gene also
appears to play a role in much more common types of
non-inherited breast cancers. These discoveries gave researchers
the ability to test for these gene mutations, but did not tell
them how to use the test.
Physicians are now facing a number of questions, including:
who should be tested; how should the information be used to mange
the patient; what are the tests really saying about level of
risk; and what are the associated costs of testing and counseling
at risk patients. Privacy issues, ability to retain insurance and
employment security are also important issues, noted Judy Garber,
M.D., M.P.H., Director, Cancer Risk and Prevention Clinic,
Dana-Farber Cancer Institute, Boston, MA
Dr. Garber is studying the implications of genetic testing
for breast cancer susceptibility (such as BRCA1). The patients
who might benefit most from BRCA1 testing have not yet been
identified, she notes. Researchers will have to determine how to
use the test results once they get them. Also, women from
families in which the BRCA1 mutation is present but who do not
have the mutation themselves are also not free of risk and will
require ongoing surveillance, she notes.
Women who do have the BRCA1 gene will face a number of
difficult choices. While there are numerous screening tests to
look for early signs of breast and ovarian cancer, there is some
debate about what measures can be taken to prevent these cancers
from developing in at risk patients. Both physicians and patients
will have to consider issues regarding the frequency of
mammograms, physical examinations and tests such as the CA-125
blood test that can detect early biochemical changes associated
with cancer growth.
Despite the significant interest of people from high risk
cancer families, it remains to be seen how many will opt for
testing as it becomes more widely available. The most data
available on predisposition testing is in the area of
Huntington's disease. Cancer doctors are hoping that experience
with this disease may provide some insight into the issues
associated with genetic testing for cancer.
A genetic test for Huntington's disease became available
recently. The test can tell with certainty if an individual is a
carrier for the Huntington's disease gene and whether that person
will develop the disease. The problem is, there is currently no
treatment for Huntington's disease.
Far fewer individuals at risk for Huntington's disease have
come forward for genetic testing than was predicted. Before the
test became available, surveys suggested that as many as 80% of
people at risk would participate in testing. However, since the
test has become available, less than half of those who could
participate in screening have done so.
The benefits of the Huntington's test are mainly
psychological. The test is definitive, which provides some relief
from uncertainty, and may helps people, regardless of the
results, better prepare for the future.
Genetic testing for cancer susceptibility is a different
matter. For one thing, a test showing that a person has a certain
gene defect shows an increased chance, not a guarantee, that the
person will develop cancer. Also, the person could still be at
some risk for a type of cancer, even if the gene defect is not
The big difference between cancer and Huntington's disease
is that preventive and therapeutic strategies do exist for a
number of cancer types. The presence of a predisposing gene could
alert physicians to conduct more frequent screening for early
signs of breast cancer for example, or could prompt dietary
changes in a person with an increased chance of colon cancer.
Breast cancer may be too complex a disorder for many women
to derive benefit from genetic testing, according to another
researcher, Funmi Olopade, M.D., Director, Cancer Risk Clinic,
University of Chicago, IL.
Dr. Olopade and colleagues analyzed the family histories of
97 women who came to the clinic for breast cancer risk assessment. The researchers found a wide variety of familial breast cancer syndromes among 1599 female members of these patients' families.Forty-six families had pedigrees consistent with identifiable
hereditary breast cancer syndromes. Another 36 families had
pedigrees consistent with familial breast cancer which did not
meet the criteria for known syndromes, and 15 families had no
obvious pattern of inheritance.
Only eight percent of these high risk families might have
benefited from BRCA1 testing, noted Dr. Olopade, who based this
conclusion on age and family pedigree data. The studies of these
families showed how complex are the patterns of cancer
inheritance. Many of the women also appeared to be at increased
risk of other forms of cancer.
"Genetic tests alone for cancer-related mutations are rarely
sufficient for determining levels of cancer risk. For women at
risk for malignancies other than breast cancer, a negative test
would be falsely reassuring. In addition, people who are tested
and found to have a cancer-related mutation will require
considerable resources, including counseling and guidance, in
establishing a plan to reduce cancer risk or ensure early
detection," noted Dr. Brian Leyland-Jones, Chairman, department
of clinical oncology, McGill University, Montreal, Quebec,
Another potential problem is that even people in very
high-risk family groups may be reluctant to receive genetic
testing and counseling. A study from Dana-Farber Cancer Institute
in Boston, MA, showed a varied amount of interest in genetic
testing in members of families at risk for Li-Fraumeni Syndrome
(LFS). Lifetime risk for numerous cancers including breast
cancer, brain tumors, and leukemia are as high as 90% in the
group of people.
The Dana-Farber researchers offered a program of genetic
counseling, medical consultation and psychological assessment to
52 family members considered at risk for LFS. Only 21% accepted
the offer, and another three percent expressed interest. The
remainder declined the offer or postponed the decision to
Age played an important role in the decision to participate,
reported Dr. Andrea Patenaude, director of Psycho-oncology
Research at Dana-Farber. The average age of those declining
counseling was 52 years, while the age of those accepting the
offer averaged 33 years. Some of those who declined said they
were concerned about losing their insurance, while others feared
a negative result form the tests. Those who did undergo the
counseling cited a desire to know their genetic risk level and
the potential risks for their children.
"The true value of advances in genetic testing will be known
only when it is combined with genetic counseling to educate
at-risk individuals so informed decisions can be made. Genetic
testing is not a benign intervention. Participants may require
time to ponder the pros and cons. Different strategies may be
needed to approach participants at different ages, noted Dr.
"What is new for oncologists are the implications of genetic
testing for family members as well as patients. Physicians must
plan carefully to handle BRCA1 testing and the results of the
testing. Policies will have to be in place to safeguard the
insurability of patients and other potential consequences of
disclosure, both intentional and inadvertent," he emphasized.
For more information on the studies cited in this article
see the May 1995 issue of The Journal of Clinical Oncology.
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