Craig Klugman, Ph.D.
My friend Nan told me the other day that her 40-year-old daughter is being tested for the BRCA 1 and 2 genes. BRCA stands for BReast CAncer. BRCA1 is found on chromosome 17 and BRCA2 is found on chromosome 13. These genes are associated with tumor suppression by repairing damaged DNA. A woman a mutation to either of these genes has a 36 or 80 percent risk (depending on the study and source) chance of developing breast cancer and a greater risk of ovarian, pancreatic, prostate, laryngeal, stomach and skin cancer. The mutation also increases risks for men.
Nan’s concern is that her daughter’s doctor “strong-armed” her into getting the test. Nan believes that the physician is getting a “kick back” for the referral. Testing costs between $300 to $3000 depending on the type of the test and one’s geographic location. There is literature and history to support her fears of companies that offer payments to physicians for testing referrals. Nan’s other suspicion comes from the fact that there is no family history of breast cancer: “Why would the doctor refer Sarah [her daughter] for genetic breast cancer testing when no one in our family has had it?” Testing recommendations usually include a family history of early onset breast cancer (before age 50) and other cancers in the family.
There is some association with this mutation and families of Ashkenazi (Eastern European Jewish) descent, which does describe the family. This population has a mutation rate in these genes of 0.25% and 0.17%, which is a much higher than risk for the general population. So perhaps the physician viewed ethnicity as reason enough for the test. Though Sarah was not offered genetic counseling as part of the process, which would have evaluated her risk factors and assisted her in making an informed choice.
There are two issues in this case on the clinical ethics front. The first is a concern over an overuse of so-called “screening” tests that are meant to detect cancers and abnormalities so they can be treated before they would have a chance to cause problems. And the second is that with genetic testing, one tests the entire family, not just the patient.
Two weeks ago I attended a talk by Otis Brawley, MD, the author of How We Do Harm: A Doctor Breaks Ranks About Being Sick in America. The thesis of his talk was that doctors prescribe and perform an increasing number of screening tests at a substantial cost. For example, a colonoscopy costs between $2,000 and $4,000 depending on geographic region. The U.S. Protective Services Task Force recommends this test every 10 years from ages 50 to 75. However, at his presentation, Brawley said that there is little-to-no evidence that increased screening improves population-level health outcomes. A few individual lives may be saved, but statistically, there is not a significant increase in the number of lives saved as a result of many common screening tests. And when it comes to screening, the population perspective is the important one. In recognition of the lack of evidence showing effectiveness, some groups have tried to change their screening recommendations but have had trouble doing so as a result of adverse reactions from their constituencies. For example, when the U.S. Preventive Services Task Force tried to change recommendations on mammogram screenings to less often and for a shorter age span, outcry prevented them from adopting the change. Adding fuel to this controversy, new data shows that individuals treated for breast tumors or even for prostate cancer may not have had a life-threatening cancer. Such individuals are likely to have died from other causes long before the cancer became a threat to their health. In some cases, the screenings themselves may cause more harm, such as increased exposure to radiation from mammograms or risks of gastrointestinal punctures from colonoscopy. And in many cases the harmful risks of treatment are consequential from disfiguring surgeries (BRCA and mammogram) to incontinence (PSA).
Regarding the second point, Nan has a real concern for her own autonomy as a result of Sarah’s test. Several years ago Nan was approached about having the very same test. She declined. “The way I saw it was that the results of the test were not going to change my behavior, so why walk around with that worry.” Once one has knowledge, there may be an obligation to act upon it. If you have a positive test, there are few options available. Nan was not going to have a double mastectomy. And if the test was negative, she wasn’t going to stop her monthly exams and periodic mammograms. So if she was not going to act on the knowledge or change her behavior, she saw no reason to get the test.
Here’s the rub: The results of her daughter’s test may give Nan results that she does not want. Mutated BRCA is a dominant inherited gene. Every child inherits two copies of the BRCA genes – one from mom and one from dad, each of whom also have two copies. If one parent has a mutated BRCA gene, there is a 50-50 chance of inheriting it. So if Sarah tests positive that means that at least one of her parents also has the gene. It also means that her own daughters have a 50% chance of inheriting the gene from her. Would she test her 5- and 7-year old daughters in that case? Although current guidelines are against screening children under 18, it’s a choice that Sarah could make.
If Sarah tests negative, then there is a 50 percent chance that each of her parents do not have the mutation—she could have inherited a normal version of the gene from each of her parents who may each still carry a mutation. This complicated state of affairs means that unlike other screenings, genetic screenings have implications for family members.
Sarah could lie and not tell her mother of the results. That choice would likely strain their relationship and if Sarah had a double mastectomy, it could be hard to hide the results from her mom. The situation would have been helped if Sarah and her mom had talked beforehand or she had gone through genetic counseling. But because of a possible financial benefit to her doctor, Sarah may have been pressured into a screening without knowledge or support to help her in thinking about the implications of the decision.
As the number of screenings available and encouraged has increased and as the number of conflicts of interest in medicine have likewise risen, the ethical discussions on this issue have not kept pace. Given the cost in dollars and in family relations, these issues must be considered.