Home delivery for everything from fresh produce to custom-selected clothing has become a way of life for many Americans. While most home-delivery conveniences are generally changing our lives for the better — giving us more time and choices — at-home genetics kits that reveal information about the risk of developing certain cancers represent a risky step in our on-demand culture.
The FDA recently gave 23andMe the green light to sell the first direct-to-consumer tests for mutations in the BRCA1 and BRCA2 genes, which are linked to serious risks of developing cancer. All a buyer has to do is ship a saliva sample to the company. Six to eight weeks later, the results are delivered through an online portal.
Mutations in the BRCA1 and BRCA2 genes were initially linked to breast cancer, hence the names (“BReast” and “CAncer”). We now know that they also increase the risk of ovarian, prostate, and pancreatic cancer. Women with mutations are at least five times more likely than women without them to develop breast cancer, and up to 20 times more likely to develop ovarian cancer. Men with BRCA2 mutations are at much higher risk of developing an aggressive form of prostate cancer.
Learning you have a BRCA mutation can be life-altering for patients and for their family members, who may also carry the mutation. In my work as a medical oncologist specializing in the management of inherited cancer, I help individuals understand their cancer risks along with strategies for cancer prevention and early detection. For most people, this is a complex and stressful conversation.
When a BRCA1 or BRCA2 mutation is discovered early, the information can be lifesaving. Women ask me: Should I have my breasts removed and, if so, when? I know I need to have my ovaries removed, but I am worried about menopause, so how long can I wait? When do I tell the man I am dating that I have a BRCA mutation? Men ask me about their risk of prostate cancer. Almost everyone worries about passing the mutation along to their children.
In our clinic, we generally set aside an hour for the initial discussion, with additional discussions over time. The same is true in similar clinics across the country. This kind of discussion and explanation isn’t something you’ll get with your 23andMe results.
Over the past decade, researchers have made fundamental advances in our knowledge of inherited susceptibility to cancer. We also now have targeted therapies, including a recent FDA approval for BRCA-associated metastatic breast cancer.
But there’s more to breast and ovarian cancer risk than BRCA1 and BRCA2. Genetic tests that I and other physicians order can evaluate up to 30 such genes. For most individuals with a strong personal or family history of cancer, insurance will cover the cost of tests a health care provider orders.
In contrast, the test available through 23andMe generates an incomplete picture (and you pay the full cost out of pocket).
A patient who came to my clinic in 2012 is an example. That was a year before the FDA warned 23andMe that it was marketing a diagnostic tool without approval, and highlighted the danger of the potential health consequences of false positive or false negative results. This patient — let’s call her Jane — told us about a very significant family history of cancer. Her sister died of ovarian cancer at 48, her mother at 62. Her maternal aunt was diagnosed with breast cancer at 49, and her maternal grandmother with colon cancer at 46. Jane had done testing through 23andMe and was under the impression that she was negative for BRCA1 and BRCA2 mutations.
Here are the problems:
Jane was not of Jewish descent. There are thousands of known mutations in the BRCA1 and BRCA2 genes. 23andMe tests for just three of them, and these three are commonly found among individuals of Ashkenazi Jewish descent. But the test is unlikely to be useful to those who are not of Ashkenazi descent; further analysis is needed. That means Jane may have a BRCA mutation even though 23andMe did not report one.
BRCA1 and BRCA2 are not the only cancer genes. Mutations in many other genes also increase the risk of breast and other cancers. These other genes are also important in understanding your risk. Families with Lynch syndrome, for example, have an increased risk of ovarian, colon, and uterine cancer due to non-BRCA genes. Based on Jane’s family history, she needed to be tested for this syndrome. Without including other genes, her testing would have been incomplete and not useful.
Family history matters. Even if Jane does not have a BRCA mutation, she still has a significant family history of cancer, which calls for enhanced screening and prevention strategies.
The best information is actionable. The best way to use genetic information to improve your health is to work with your health care team to interpret test results in the context of personal and family history.
Jane’s misunderstanding of her 23andMe results led her to underestimate her cancer risk. We tested her for 25 different cancer-related genes. She did not have a specific mutation in any of these genes. Even so, we recommended increased screening and prevention options on the basis of her strong family history. We also recommended that other members in her family be tested to see if we could identify the family’s specific genetic risk.
Genetic testing can be lifesaving, but it must come with all the facts — which are mounting by the day — and appropriate professional support to help individuals live and plan for the best chance of a healthy life, no matter what the results reveal. That’s something a mail-order kit just can’t do.
Susan Domchek, M.D., is executive director of the Basser Center for BRCA at the University of Pennsylvania and a medical oncologist in Penn’s Abramson Cancer Center. She reports having received honoraria from AstraZeneca, Clovis, and Bristol-Myers Squibb.