Best Use of Breast Cancer Genetics Presents Clinical Challenge

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 Institute.

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. "There’s a whole ton" of mutations in the BRCA1 and BRCA2 genes that relate to breast cancer, he noted. "You can’t simply look in one place" to determine an individual’s 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 test."

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 "don’t 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 place."

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.