On October 8th MSNBC published an article by Arthur Caplan, Ph.D. on genetic tests for breast cancer.
The following is a response by Jeff Gulcher, M.D., Ph.D, Chief Scientific Officer at deCODE Genetics.

Arthur Caplan stresses caution in the application of the new genetic risk tests for common diseases and I certainly agree that genetic testing should be applied with care. However, he goes too far when he says that the new deCODE BreastCancer genetic risk test is only useful for women who have two or more close relatives with breast cancer, is not based on large enough studies to be accurate, and is not regulated.

There are two major types of breast cancer: the rare, early onset form that occurs in certain families and for the detection (for which the Myriad Genetic test is well suited), and the common form which accounts for 95 percent of breast cancer. The vast majority of women who develop breast cancer do not have the conventional risk factors of family history, pregnancy history or breast density. Unfortunately, many of these women were likely considered to be of average risk before their cancer was found. Therefore, they were not even offered screening with breast MRI which detects two to three times more cancer at an earlier stage than mammography alone, or preventive measures such as tamoxifen treatment which can cut down cancer rates by 40 to 50%.
To date, the healthcare system has not been as good as it would like to be at predicting which women are at higher risk of the common forms of breast cancer: But we at deCODE and others have invested years of research and tens of millions of dollars to find other factors that can complement the conventional factors. Our efforts have paid off, because there are 7 genetic markers, easily and accurately measured from a cheek swab, that define most of the genetic risk for the common forms of breast cancer. The test defines risk from 0.4-fold to 4-fold compared to the general population risk (the average woman of European ancestry in the US has a lifetime risk of 12%). Based on this test alone, 10 percent of women have risks ranging from 1.4- to 4-fold, and would account for about 17 percent of breast cancer cases. Five percent of women are at more than 2-fold average risk, and the 1 percent are at 3-fold risk, so the risk is substantial for a significant portion of the population.

This risk is independent of family history and other conventional risk factors and therefore may identify some women as having higher risk even if breast cancer does not appear to be in their families. So Arthur Caplan is fundamentally incorrect in stating that only women with a family history of breast cancer would benefit from genetic testing. That may be true for traditional genetic diseases like Huntington’s disease and the rare highly familial form of early breast cancer addressed by the Myriad test, but the new tests for common diseases define risk beyond family history.

Each of the genetic markers in this risk test have been replicated in between 5 and 30 different populations in studies by deCODE genetics, the National Cancer Institute, and UK Cancer Research. These studies have been published in the most prestigious, peer-reviewed journals, including Nature Genetics and the New England Journal of Medicine. Altogether almost 100,000 patients and controls have been studied to define the marker risks. We made this test available for physicians to order for their patients through our reference laboratory which is regulated under CLIA by the US Federal government.

However, it is important to emphasize that the test does not diagnose breast cancer: it is simply a means of assessing personal risk of the disease, much more analogous to an LDL-cholesterol test for assessing heart disease risk than traditional genetic tests for purely genetic rare disorders like that for Huntington’s disease. That is, women at higher risk based on deCODE Breast Cancer are not destined to develop breast cancer. They may have a 20 to 36 percent lifetime risk for developing cancer (versus baseline risk of 12%). Women at lower risk are not immune from breast cancer and therefore would still be regularly screened with mammography. Women at higher risk above a certain threshold may benefit from more intensive screening using breast MRI on top of mammography, as recommended by the American Cancer Society. Also, certain medications such as tamoxifen which blocks the estrogen stimulation of breast cancer cells are approved by FDA to reduce breast cancer risk for women at higher risk.

In summary, this test may reclassify as higher risk some women who were previously considered to be of average risk, contributing to earlier detection and more focused prevention strategies. In fact, this test together with family history could define as higher risk the roughly 20% of women who may account for 35 to 40% of future breast cancers.

Looking at the big picture, about 5 percent of the health care budget is used for diagnostics and most of the rest is for therapeutics. Much money has been invested in the development and use of new expensive therapies for women with advanced cancer. But individual women and our healthcare system may both benefit from the increased use of risk diagnostics to help to focus on women at higher risk and thus diagnose cancers earlier rather than later, saving lives, suffering, and money.

Anyone who wants to hear some real stories from real people about how genetic tests like this may improve healthcare can find them on this blog.

Jeff Gulcher MD PhD
Chief Scientific Officer
deCODE Genetics