Last week, the Icelandic company deCODE Genetics began offering a new breast cancer gene test that it claims measures genetic risk for the common forms of the disease. The new test assesses seven single-letter variations (a.k.a., single nucleotide polymorphisms) in the human genome that researchers have linked to higher risk of breast cancer. The average lifetime risk for women of European descent is 12 percent. The company claims that its new test can tell a woman if her lifetime risk of breast cancer is as low as 5 percent to as high as 48 percent (from 0.4-fold to 4-fold lifetime risk). deCODE notes that the test has not yet been validated for women of other ethnic backgrounds.
Not everyone is happy with deCODE's test. Some biomedical paternalists want the Food and Drug Administration to forbid deCODE from selling it. "Sadly, the tests deCODE and other companies are offering are more likely to empty family pocketbooks and leave women with a false sense of security than they are to prevent breast cancer," writes University of Pennsylvania bioethicist Arthur Caplan. "There is at least a significant chance this test will could falsely reassure some women and alarm others," said Eric Winer, a breast cancer expert at Harvard Medical School to the Washington Post. "I fear for many women the results could be quite misleading." The Post also reported that University of Washington geneticist and breast cancer expert Mary-Claire King said, "I wouldn't recommend to anyone that she have such a test. I certainly wouldn't want my daughter to have such a test." These opponents argue that the test has not been sufficiently validated and that it could result in more harm than good as women spooked by false positive tests seek invasive treatments.
deCODE Genetics claims that its new test can identify "the roughly 5 percent of women who are at a greater than 20 percent lifetime risk of the common forms of breast cancer (about twice the average risk in the general population), and the 1 percent of women whose lifetime risk is roughly 36 percent (about three-times average)." American Cancer Society guidelines recommend that women whose lifetime risk as currently measured by some standard risk assessment models is greater than 20 percent should be annually screened using more sensitive magnetic resonance imaging (MRI) in addition to mammography. The idea is women who test as being at a higher risk will be more vigilant about detecting any cancer early on, enabling them to receive treatment before the cancer has spread. In addition, some higher risk women may choose to begin taking the drug tamoxifen, which clinical studies show can dramatically lower the risk of breast cancer.
The deCODE test is based on published scientific research that shows that certain variants of each of the seven SNPs confers a greater risk of breast cancer. While it is true that some of the research has not been replicated by other investigators, one should keep in mind that this is not a drug, but a risk assessment test. The test does not detect cancer; it is more like a test for cholesterol levels that are associated with higher risks for heart disease. For example, patients whose total blood cholesterol level is 240 mg/dl or more have double the risk of a heart attack as someone with a cholesterol level of 200 mg/dl or lower. Just as having higher cholesterol levels does not guarantee a heart attack, an indication of higher genetic risk does not presage breast cancer.
Diagnostic tests, however, do not have to be perfect to be useful. For example, the false positive rate in the widely used prostate specific antigen (PSA) test is between 15 and 30 percent, which means that for every four to six men who test positive for the disease only one will actually have cancer. However, since the advent of the PSA test, the death rate for prostate cancer has fallen from 39 per 100,000 men in 1990 to 27 per 100,000 in 2003. Although many attribute a good bit of this decline to PSA testing, it is still not known for sure that prostate cancer screening has actually resulted in a reduction of prostate cancer mortality. Yet the PSA test has been used for 22 years. As the limitations of the older PSA test became more evident, researchers have been competing to develop more accurate prostate cancer detection tests.
What about the claim that the deCODE breast cancer test could result in more harm? The chief concern is that women would be unnecessarily alarmed by a result suggesting higher risk. But how have women responded to other breast cancer tests, specifically the BRCA1 and BRCA2 gene tests? Women with an altered BRCA1 or BRCA2 gene are 3 to 7 times more likely to develop breast cancer than women without alterations in those genes. A recent study looked at how 215 women who had undergone BRCA gene testing reacted to their results. The study found that after four years none of the three groups—those who tested negative, positive, and inconclusive—had "adverse psychological consequences" from BRCA testing. In fact, the study found that "in all three groups, the women were less worried than before they were tested."
As the era of widespread genetic testing unfolds over the next decade, physicians and citizens will become increasingly familiar with how to interpret test results. Testing companies also have an interest in making the risk information they provide understandable and useful to their clients. "A lot of women are afraid of breast cancer. They just don't know what their risk is," said Kay Wissmann of the Breast Cancer Network of Strength, a Chicago-based advocacy group, to the Washington Post. "For those women who choose it, this test could provide information that could potentially help women make better decisions. It could empower them."
Ronald Bailey is reason's science correspondent. His book Liberation Biology: The Scientific and Moral Case for the Biotech Revolution is now available from Prometheus Books.