There are frequent discussions in the media, within scientific and medical communities, and among individuals about what genetic testing means or might mean, particularly in the age of precision medicine. The issue becomes more complicated when the genetic testing under consideration is ethnicity-specific, because when it comes to genetics, ethnicity does matter. Genetic variants that cause a particular disease in one ethnicity may not in another. Genetic testing for BRCA1/BRCA2 mutations and breast cancer risk is well-established in the medical community, but what does that mean for individuals considering testing?
One example of this discussion comes from a New York Times opinion piece, The Breast Cancer Gene and Me , by Elizabeth Wurtzel, author of Prozac Nation and an Ashkenazi Jewish woman who was recently diagnosed with breast cancer due to a pathogenic BRCA mutation. The article is very much an opinion piece, coming at a time in the author’s life when, naturally, her opinions about breast cancer were very strong. She concludes that all Ashkenazi Jewish women should be tested for BRCA mutations, given their known elevated risk status.
Wurtzel has a point: doctors and scientists do know more about which BRCA mutations are causal in Ashkenazi Jewish women as opposed to many other ethnicities. However, while doctors and scientists know how to identify predisposition to cancer in these women, that knowledge is incomplete. There are still genetic variants of unknown significance to consider for women of all ethnicities. And even causal mutations do not have complete penetrance – meaning that having a mutation does not guarantee breast cancer, though it does greatly increase risk. A causal mutation would only increase lifetime risk by 56% to 84% of a baseline risk on the order of 1% or less, meaning that an individual's risk could be at the lower or higher end of that spectrum, with no guarantee of breast cancer. Just as many women are diagnosed with breast cancer even without having any known causal BRCA mutations. In that respect, the opinion piece does get the numbers correct, as well as providing useful links.
However, the decision to get BRCA testing is something that any woman with a family history of breast/ovarian cancer or Ashkenazi ancestry should weigh carefully; she should research the numbers and take stock of the choices she might make if test results indicate a known pathogenic mutation . Preventative surgery is a big step, as Angelina Jolie documented in her own New York Times opinion piece, My Medical Choice , reflecting on her decisions when faced with a BRCA mutation and her family history of breast cancer that claimed her mother's life. Ms. Jolie's piece is a reminder that this disease and these mutations do not only affect Ashkenazi Jewish women – it’s merely that scientists have a better grasp on which mutations are pathogenic for that community.
Wurtzel's Times piece is well-written, well-researched, and quite powerful. Certainly, any woman who wants BRCA testing should have that option without insurance limitations. This is especially relevant for Ashkenazi Jewish women, where scientists have a clearer understanding of which variants are actually pathogenic and thus, what their test results might mean. Indeed, according to follow-up Times Letters to the Editor , efforts are underway to make BRCA testing available to all Ashkenazi Jewish women over age 25.
But, as a Jewish woman of Ashkenazi descent and a geneticist myself, I do balk at the idea of forcing, or even strongly recommending, everyone to be tested for something that is not fully penetrant, when the prevention measures and the psychological distress related to carrying a mutation are quite extreme. There’s an ethical decision-making process that must weigh the concepts discussed in the seminal ethics text Beauchamp and Childress’ Principles of Biomedical Ethics : Respect for Autonomy, Beneficence, Non-maleficence, and Justice .
While a detailed ethical dissections of the four concepts is outside the scope of this piece, the key aspects of choosing whether to get genetically tested are (1) whether getting the disease is guaranteed (fully penetrant, no variants of unknown significance), (2) how severe the disease is, (3) whether it is actionable (and how severe that action is), and (4) what the age of onset is.
For example, screening for Tay-Sachs disease  has been widely adopted because it is severe or lethal, it has an early onset--during infancy--and prenatal screening has made it preventable. Tay-Sachs is a disease that disproportionately affects Ashkenazi Jewish individuals, in marked contrast to breast cancer, which affects all ethnicities, but the causal mutations are better known among the Ashkenazi community.
Testing for Huntington’s Disease , on the other hand, is very much a personal decision because its onset is late in adulthood and there is no prevention or treatment.
There are many other examples involving Mendelian diseases like Tay-Sachs and Huntington’s, which are inherited in a fairly straightforward fashion, as well as complex diseases, which are not. Cancer is a complex disease, with many contributing genes and incomplete penetrance of causal risk mutations.
For breast cancer, family history and/or pathogenic BRCA mutations increase risk of both early-onset and lifetime cancer. But they do not guarantee cancer. Even should cancer occur, it may be years or decades after the time a woman chooses to be tested. The only preventative option is a double mastectomy , which is a highly invasive surgical procedure, not without its own risks. Further, though this procedure greatly reduces the risk of breast cancer, as there is not much breast tissue left, it does not completely eliminate it, nor does it eliminate the risk of ovarian cancer brought on by the same BRCA mutation. The only option for reducing the BRCA-associated risk of ovarian cancer would be to undergo further invasive surgery, thereby risking early-onset menopause. That’s a significant amount of invasive surgery to reduce a risk that is not 100%, which is why each woman must carefully weigh her personal decision in the matter based on family history, as well as genetic testing.
Certainly, it is important to be aware of the risks, and it is a very difficult situation that Ms. Jolie and Ms. Wurtzel found themselves in. Should someone desire testing, particularly for Ashkenazi Jewish women, where we have a better idea of the causal variants, BRCA testing should be available, accessible, and not prohibitively expensive. Ms. Wurtzel's piece is an important call to insurance companies to cover testing for those Ashkenazi Jewish women who want it.
However, choosing to test for a cancer risk gene remains a highly personal choice that should be taken based on family history and after discussion with a genetic counselor. Because even if the result seems clear, the resulting path may not be as straightforward as one might hope.
 Beauchamp TL and Childress JF. Principles of Biomedical Ethics. Seventh Edition. USA: Oxford University Press; 2013.
*An earlier version of this article was originally posted on the author's blog: Scientifically Transmitted Information (http://stiscience.wordpress.com)