We CAN handle the truth

The BRCA genes were discovered in 1994 and 1995 but when you visited your doctor those years, or even when you visited anytime until the early 2000s, chances are that your doctor did not recommend that you test for mutation on the BRCA genes. Why?  Because the paternalistic feeling of much of the medical community was that women who might be carriers of mutations couldn't handle knowing their risk.  In fact, in 1998 an esteemed panel of experts convened a conference at Stanford University to decide what to do with the newfound ability to test for these genes.  Their conclusion?  Genetic testing should not be recommended:

"Genetic testing for mutations in BRCA1 and BRCA2, which are associated with increased lifetime risk of breast and ovarian cancer, may become the first widely accessible genetic testing for common adult onset diseases. The Stanford Program in Genomics, Ethics, and Society convened a multi-disciplinary Working Group that, in a lengthy process, studied the ethical, legal, and social issues arising from testing. The Working Group concluded that testing for mutations BRCA1 and BRCA2 genes is not appropriate for widespread clinical use or population screening, but may be beneficial in some circumstances—for example, in families experiencing multiple cases of cancer. Testing would raise fewer problems if definitive preventive interventions were available for those with the mutations, and if society better protected people with genetic risk of cancer. Even with current limitations, competent adults at high risk may choose to participate in a testing program. Such programs, however, must meet rigorous standards, including genetic counseling, confidentiality, and follow-up care. Health insurance should pay for all components of testing when it is appropriate; governments should take steps to protect people from discrimination and invasions of their privacy, as well as from the offering and advertising of inappropriate testing. We call on governments, researchers, insurers, testing laboratories, healthcare providers, and individuals to take important steps to help ensure that testing for BRCA1 and BRCA2 mutations, surely a forerunner of the many forms of genetic testing that will follow, improves people's lives, and does not diminish them."

In fact some doctors went so far as to test women for BRCA mutations but then refuse to tell them the results because they thought the knowledge would be harmful.  Other experts at that time concluded: "there are no known methods for preventing breast or ovarian cancer that would be particularly important to women with versions of these genes."  Essentially, doctors were throwing up their hands and saying they didn't have any good options and that knowledge was a dangerous thing.

Fortunately, times have changed.  Medical experts now agree that genetic testing for BRCA genetic mutations saves lives and alternatives are available.  And the feared phycological harms have not materialized.  Numerous studies of at-risk women have been conducted over the past decade and the consensus is: women can handle the truth!" Studies of individuals receiving such genetic information suggest that those who do not carry 'at-risk' genotypes derive psychological benefits, while those identified as 'at risk' show no adverse effects," proclaimed a 2009 study in the British Journal of Psychiatry.

Does this mean there are no phycological impacts from genetic testing and discovering you are at genetically high risk for cancer? No.  Learning you are at high risk for cancer causes stress, no doubt.  Joi and the other men and women profiled in Positive Results candidly discuss the emotional toll knowing about a BRCA mutation can take.  But they also show how this knowledge can be empowering, allowing them to escape the fate of cancer that has stricken other members of their family.

Earlier this month, Ronald Bailey, science correspondent for Reason and author of Liberation Biology: The Scientific and Moral Case for the Biotech Revolution posted Bioethicists Can't Handle the Truth, where he discussed the conundrum of testing for genetic markers for Alzheimer's disease and likened the current state of affairs to the recommendations for genetic testing for BRCA mutations in the late 1990s.  Specifically, bioethicists and genetics professionals generally do not recommend testing for increased risk of Alzheimer's disease because at this time medical science has no cure.  Again, the rationale is paternalistic, if there is no treatment option, why subject individuals to the increased emotional stress of knowing they are likely to develop this disease?

The reason this is currently a hot topic of conversation is that personalized genomics – knowing the content of your individual DNA genomic sequence – is now affordable and widely available to the general public, made possible by major advances in technology and scientific knowledge over the past several years. In fact, Science magazine called the advances in personalized genomics the "breakthrough of the year" in 2007.

But in fact the "breakthrough" in personalized medicine came in 1994 with the discovery of BRCA1. This is why researchers and commentators alike are looking to the hereditary breast and ovarian cancer community for answers on how consumers cope with genetic knowledge.  BRCA mutation carriers are on the front line of personalized medicine.

And yet, the analogies are not always appropriate.  Is knowledge of increased risk for breast and ovarian cancer really the same as increased risk for Alzheimer's disease?

No. Knowledge of a BRCA mutation provides a patient with options for avoiding disease development.  Preventive surgery works for BRCA carriers: it reduces risk of disease development and improves a woman's chances of living a long and healthy life.  And even if patients choose surveillance for breast cancer, research shows that the disease is likely to be caught early and be curable.  Breast MRI is so effective at detecting early breast tumors that Dr. Andrew D. Seidman, MD, member of the American Society of Clinical Oncology Cancer Communications committee said:

"The favorable overall survival in all high-risk groups reported suggests that careful MRI screening is not only superior to mammography alone, but may be an attractive alternative to risk-reducing prophylactic mastectomy for some women."

On the other hand, options for preventing Alzheimer's if a patient knows he is at high risk are limited.  The National Institute on Aging is blunt in its assessment of Alzheimer's treatment and prevention: "No treatment has been proven to stop [Alzheimer's disease]."  Current recommendations for preventing Alzheimer's include:

• Avoiding smoking
• Eating a balanced diet rich in vegetables, fruits and lean protein, particularly protein sources containing omega-3 fatty acids
• Being physically and socially active
• Taking care of your mental health

Although considerable resources are being poured into Alzheimer's research, there are currently no quantitatively effective prevention strategies, although there are a number of drugs now available that may slow progress of the disease for a period of time.

Another reason that testing for genetic Alzheimer's markers is different than BRCA testing concerns the ability of the test to predict the likelihood of disease development.  A woman who tests positive for a BRCA mutation knows that she is definitely at increased risk for developing both breast and ovarian cancer and she knows that this risk falls within a well-defined if rather broad range (breast cancer risk between 45 percent and 87 percent and ovarian cancer risk between 11 percent and 56 percent) based on a decade and a half of research.

Disease prediction with Alzheimer's genetic markers is unclear as was discussed in Genetic Markers for Alzheimer's Diseases: Are They Ready for Prime Time?:

"Although the findings in this [new study in the journal Neurology] are of considerable interest, their application to everyday clinical practice is limited. For individuals seeking genetic information about Alzheimer disease, the predictive value is unclear, unless the individual is from a family carrying one of the rare autodominant APP or presenilin mutations. 

For example, for many years, we have known that information about APOE genotype is neither necessary nor sufficient to predict a diagnosis of Alzheimer disease. Some people with the APOE4 mutation, which has been associated with an increased risk for disease, will never get the disease in their lifetime, and many without the APOE4 mutation will get the disease. That is why experts have been reluctant to recommend these types of "risk" tests as individual predictive tools -- there is concern that some people would be falsely alarmed by their test results while others would be falsely reassured. (It is interesting to note, however, that systematic studies of people who choose to obtain their APOE genetic results do not seem to show any obvious negative psychological consequences from these results."

As the burgeoning field of personalized medicine advances both experts and the public will continue to look to the hereditary breast and ovarian cancer community as trailblazers in this brave new world.  History will record that this community rose to the challenge presented by this new knowledge to improve their lives and limit the impact of two deadly diseases on this and future generations.


This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License.