Breast Cancer Gene Test Disputed

By Abram Katz

A one-minute television ad masquerading as a public service announcement about hereditary breast cancer over-simplifies and exaggerates the risk of the disease, omits important caveats and encourages women to take an expensive genetic test that most do not need, doctors and genetic counselors contend.

Myriad Genetic Laboratories of Salt Lake City, Utah, began the breast cancer campaign on Sept. 10, with television and radio advertisements urging women to "be ready for breast cancer" by undergoing a $3,100 test that Myriad has under patent.

At issue are two genetic mutations, BRCA 1 and BRCA 2, that are passed through generations and significantly increase the lifetime risk for breast and ovarian cancer.

Because of Myriad’s patents, it is the only company that can offer tests for the two flawed genes.

However, only 5 to 10 percent of breast cancers are hereditary, cancer specialists said.

And the Myriad test, called BracAnalysis, could miss cancer causing mutations in a small percentage of women, and suggest a risk where none exists, according to a study in the Sept. 27 Journal of the American Medical Association.

Moreover, the genetics of hereditary cancer are exceedingly complex and many primary care doctors might not be able to judge test results or advise patients knowledgeably, said Dr. Molly Brewer, associate professor of gynecology in the University of Connecticut Health Center’s Neag Comprehensive Cancer Center.

"Most doctors are not familiar with genetic cancer. Publicizing the test is good, but it’s not something everyone should be tested for. Advertising to patients that they should be genetically tested is inappropriate," Brewer said.

Dr. Gregory C. Critchfield, president of Myriad Genetic Laboratories, said the television and radio ads are intended to make women with a "family history" of breast or ovarian cancer aware of the test and its importance.

"It’s designed to raise public awareness of hereditary breast and ovarian cancer and to encourage women to talk to their health care providers," he said.

"Actually, they’re ads by a company with an exclusive patent that has an incentive to sell their tests," said Ellen T. Matloff, director of cancer genetic counseling at the Yale Cancer Center.

The cost of the BracAnalysis blood test is only covered by health plans if the woman has real risk factors for hereditary cancer.

"The television ad doesn’t mention any of the risk factors for hereditary breast and ovarian cancer, or that a minority of breast cancers are hereditary," she said.

"Only one in 10 breast cancer cases are hereditary, and only one in 400 people carry one of these mutations," Matloff said.

The ads have caught the attention of Attorney General Richard Blumenthal, who has subpoenaed Myriad for information about the ads, the test and other subjects.

Critchfield said Myriad is cooperating with Blumenthal and is assembling the requested documents.

"They seem to exaggerate, and oversimplify the benefits of taking the test," Blumenthal said.

The ad consists of women talking into the camera. "Breast cancer runs in my family," says one. "My mother," says another. "My grandmother," a third.

Then a woman says, "I wondered if it would be inevitable."

The first woman returns to say, "I found out it doesn’t have to be. I found my risk though BracAnalysis."

The problem with the ad up to this point, is that having family members with breast cancer does not mean the cancer is hereditary, said Robin Schwartz, assistant professor of genetics and developmental biology and pediatrics at the UConn health center.

Signs of hereditary cancer include multiple cancers in a family and early onset of breast cancer, Brewer said. While most breast cancer occurs in post-menopausal women, hereditary breast cancer often appears in women 25 to 40 years old, she said. These cancers also usually run down one side of a family.

Then a woman in the ad says, "BracAnalysis is a blood test that has helped thousands of women find out their risk for breast and ovarian cancer."

The first woman again: "After BracAnalysis I realized I could do something now."

The fact is that about 1 in 8 women in the U.S. will develop breast cancer. Risk factors include age, age at the first menstrual period and age of first live birth. BracAnalysis could identify a much less likely cause of breast cancer.

Women with normal genes face a 1.7 percent lifetime risk of ovarian cancer and a 12 percent lifetime risk of breast cancer, Brewer said.

Women with a BRCA 1 mutation have an 85 percent risk of breast cancer and a 40 to 60 percent chance of ovarian cancer.

However, the number of women carrying mutations of BRCA 1 or 2 is so small that their cancers comprise 5 to 10 percent of breast cancers.

The rate of the BRCA 1 mutation is about 8.6 percent, and BRCA 2 is about 5 percent, studies suggest. This means that BracAnalysis is of no use for at least 90 percent of women in the U.S.

Of the small remaining pool, the BracAnalysis test does not detect all BRCA mutations, either. Researchers at the University of Washington found that genetic testing in the U.S. for BRCA 1 and 2 mutations — necessarily performed by Myriad — missed about 12 percent of the cancer-predisposing genes, according to the JAMA report of Sept. 27.

Schwartz said BracAnalysis test results require expert interpretation. The possible results are:

• Positive for a "deleterious mutation" of BRCA 1 or 2.
• Positive for a genetic variant suspected of being deleterious.
• Positive for a genetic variant that is not believed to cause cancer.
• Positive for a genetic variant of uncertain significance.
• Negative for mutations.

Each of these findings presents the women who was given the test with a quandary, Schwartz said.

Contrary to the Myriad ad, medical options for women with confirmed BRCA 1 or 2 mutations are limited.

The safest, though most disruptive option, is removal of both breasts and the uterus. Many women instead opt for frequent cancer screening tests.

But these results have ramifications for more than the one woman patient, Schwartz said.

"If someone approaches this as ‘just a blood test’ they may be unaware of the implications for other family members," she said.

Positive results mean that the patient’s siblings and children may also carry the mutations. Should the woman notify all affected? How will they react? What about estranged family members?

If the finding is of "uncertain significance," what should the woman do?

Matloff said, "Recently I consulted with a woman who had a finding of variant of uncertain significance, and she was about to get both breasts removed."

A double mastectomy was not indicated, as it was not clear whether the mutation was even harmful, she said.

Blumenthal said the tone of the ad is also troublesome. The test might give some women a false sense of security, or convince them to undergo unnecessary measures, he said.

Furthermore, a general practitioner can request the test without receiving appropriate training, Blumenthal said.

Critchfield said physicians can depend on medical society guidelines or take continuing medical education courses. "This is a service. It allows doctors to learn what their societies are saying," he said.

"The importance of discussion between the patient and health care worker cannot be overemphasized," he said.

However, Myriad does not offer training on the use, application or interpretation of the test, he said.

Still, the Myriad campaign could help thousands of women, Critchfield said. "This is a very important story to get out into the community. There is a large number of women at risk for hereditary cancer," Critchfield said.

Critchfield said 97 percent of carriers of BRCA 1 or 2 mutations do not know it. Experts questioned the basis for that number.

Blumenthal said the ads apparently overstate the number of women who carry the mutated genes, or who could benefit from the test.

In addition, unlike ads for pharmaceuticals, the Myriad ad does not mention that hereditary breast and ovarian cancers amount to a very small percentage of the total, that the test may yield ambiguous results, and that it carries a risk of false positive and negative results, Blumenthal said.

"The ad appears to be a public service announcement. That’s very concerning to us. The content and tone suggest it is a public service announcement," he said.

The subpoena was filed under the aegis of the Department of Consumer Protection. "If Connecticut finds that the ads are deceptive, we can seek restitution for consumers, and also seek fines and penalties," Blumenthal said.

"Promoting awareness of ways to prevent cancer is very good. These ads are not efforts to prevent or reduce risk," he said.

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