WASHINGTON--Genetic research has produced a growing body of
information about the mutations related to breast cancer, but, so
far, "no clear algorithm" to help clinicians decide how to
use the new findings in the interests of patients, reported Francis
S. Collins, MD, PhD, director of the National Human Genome Research
Addressing the 28th National Conference on Breast Cancer of the
American College of Radiology, the man who heads the agency charged
with mapping the entire human genome declared that "pretty
significant" issues complicate the decisions of women who wish
to use the new discoveries to assess their personal risk of breast
cancer. Such issues also affect the physicians and other
professionals who must advise and care for these women.
First, technical issues in gene testing remain substantial.
"Theres a whole ton" of mutations in the BRCA1 and
BRCA2 genes that relate to breast cancer, he noted. "You
cant simply look in one place" to determine an
individuals risk. A complete sequence of both genes now costs
$2,500 and is often not covered by insurance. Costs will come down,
however, Dr. Collins believes, with the advent of new techniques able
to test for many mutations at a cost of only $100.
But even when it is more reasonably priced, genetic testing will be
subject to problems of accuracy. "Mistakes could be very
serious," he said, and the clinician and patient cannot always
be sure of finding a commercial lab "where you can trust the
Dr. Collins next turned to the issue of selecting appropriate
candidates for testing. In breast cancer patients from families with
three or more breast or ovarian cancers, the chance of having a BRCA1
mutation is between 13% and 36%; among breast cancer patients without
a strong family history, it is only 3%.
Although much important genetic research was done in very big
families, most people who want testing lack large numbers of
relatives. Taking a "careful family history," therefore,
becomes crucial to selecting those who might benefit from genetic
testing, he emphasized. In addition, it is "entirely possible
that some mutations are worse than others," he said.
What Does the Mutation Mean?
Once a variant is found, Dr. Collins asked, "Does that finding
have clinical consequences?" At this point, researchers do not
know for sure what all mutations mean in individual, clinical terms,
and "uncertainty about the best medical management" of
individuals carrying known breast cancer mutations further
complicates the picture.
Researchers "dont yet know the effectiveness" of
prophylactic mastectomy or regular mammography in forestalling
cancer, he said, and have even "fewer good ideas" about
managing carriers risk of ovarian cancer.
Fear that genetic information will be used against them dissuades
many from seeking genetic testing, he added. Although people covered
by group health insurance plans cannot legally be penalized because
of genetic information, individual policy holders may have no such
protection. The "very messy business of genetic discrimination
is really a civil rights issue," Dr. Collins said, adding that
"we should not rest until adequate protections are in
In addition, occasional unscrupulous commercial interests have used
fear tactics to try to sell genetic testing among groups with high
rates of highly publicized mutations, such as Ashkenazi Jews. For
this and other reasons, he believes that testing should ideally be
done under research auspices.
"We desperately need new information" about the
relationship of mutations to cancer risk and about how best to manage
carriers before genetic testing can become a useful routine tool for
clinical care, he concluded.