Editor’s Note: The scientist who identified the BRCA1 gene has recommended that all women get tested for genetic mutations[1,2]—but who will pay for it?
It’s been called the “Angelina Jolie effect.”
Shortly after the actress announced that she carried a genetic mutation that dramatically increased her odds of developing breast and ovarian cancer, referrals for both genetic counselling and BRCA testing rose dramatically. As reported recently at the 2014 Breast Cancer Symposium, twice as many women were tested for BRCA1/2 mutations in a North American clinic in the 6 months following Jolie’s announcement than the clinic normally handled. In the United Kingdom, the number of referrals for genetic counselling and testing in the UK increased two and a half times in the months that followed Jolie’s announcement, as compared with the same period in 2012.
It is well established that inherited mutations in BRCA1 and BRCA2 genes can predispose women to an extremely high risk of developing breast and ovarian cancer, but hereditary risk accounts for only a small fraction of these cancers in the general population. These particular mutations are rare, found in about 2% to 4% of women,[6,7] and tend to be observed in those with a family history of breast and ovarian cancer as well as certain subgroups.
But should all women be tested, even if their risk of carrying the mutation is seemingly low? And if so, who should bear the cost of testing and follow-up?
Jolie had a BRCA1 mutation coupled with a strong family history. Her mother and maternal grandmother died of ovarian cancer, and her aunt died of breast cancer in May 2013, shortly after Jolie revealed that she had undergone preventive surgery. For women with strong family histories, testing makes sense, especially when breast cancer occurs before the age of 50, according to current guidelines.
However, a trio of scientists, including one whose laboratory first identified the BRCA mutation and its relationship to the risk for breast and ovarian cancer, are calling for BRCA testing to be made routine.
Mary-Claire King, PhD, professor of genome sciences, University of Washington, Seattle, and co-authors Ephrat Levy-Lahad, MD, director of the Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel, have recommended that genetic screening for BRCA1 and BRCA2 should be routinely offered to every woman at about the age of 30.[1,2]
Dr King was the recent recipient of the 2014 Lasker-Koshland Special Achievement Award in Medical Science for her work in identifying the BRCA1 gene mutation. Writing in a JAMA viewpoint article, she and her coauthors urge that screening be offered to all women because “many women with mutations in these genes are identified as carriers only after their first cancer diagnosis because their family history of cancer was not sufficient to suggest genetic testing. To identify a woman as a carrier only after she develops cancer is a failure of cancer prevention.”
Needless to say, not all experts share her views. Some question whether this type of screening is really warranted given the low incidence of the mutation in the general public, and whether the benefit of universal screening outweighs the harms.
Universal Testing Would ‘Break the Bank’
But what Dr King didn’t mention was how the cost of screening figures into the picture.
In an interview with the New York Times, Dr King reiterated her recommendation and noted, “You only need to be tested once, and the vast majority of women will not have a mutation and can go about their life. The actual cost is minimal.”
However, it seems as though the price tag attached to universal testing would be anything but minimal. “That cost could run in the billions of dollars in the United States,” said David H. Finley, MD, national medical officer, Enterprise Affordability and Policy at Cigna, “if all women follow her advice and get tested.”
Based on the number of women who fall into the age bracket loosely defined by Dr King, as well as the current average cost of testing, the total cost could reach upwards of $170 billion. “And that is only the cost for the test itself,” Dr Finley said. “It doesn’t include follow-up costs, such as genetic counselling or actions that may be taken based on the test results.”
The breakdown of cost depends on the number of women who would actually step up to the plate and opt for screening, along with the price of the test. This is all hypothetical, Dr Finley stressed, because no formal evaluation has been conducted, and it is difficult to say how many women would even be interested in getting screened.
But using ballpark figures, there are anywhere from 80 to 100 million women who might fit into the age demographic for testing, depending on the designated lower or upper age bracket. If all of those women were screened, with the cost averaging $2000 for each test, the total would be somewhere around $170 to $200 billion, Dr Finley calculated.
Other costs would need to be calculated in as well, depending on what testing revealed. In some cases, Dr Finley explained, follow-up interventions would be cost-effective because they would dramatically reduce a woman’s risk for cancer and the subsequent expense of treatment. But for others, the results might prompt them to undergo unnecessary medical procedures.
Basically, for most women, testing would not be helpful and could be quite harmful as well, he added. “Payment for the tests would also be out of pocket if women didn’t meet the criteria for testing that is in place right now.”
Dr Finley pointed out that Cigna, in line with other insurance providers, will cover testing for BRCA1 andBRCA2 gene mutations that occur among women with known risk factors, using criteria outlined by the National Comprehensive Cancer Network (NCCN). Guidelines from other associations vary slightly,[10,11] but there aren’t any professional groups calling for universal testing, or anything close to it.
The US Preventive Services Task Force also reaffirmed its 2005 guidelines last year, and recommends against routine genetic counselling or BRCA testing in a low-risk population.
Universal testing would “break the bank,” said Joy Larsen Haidle, MS, CGC, president-elect of the National Society of Genetic Counselors, and a genetic counselor who specializes in hereditary cancers.
“Not all patients who test positive for a mutation will choose to do the same thing,” she said. “But broad-based screening makes it more difficult to help patients choose the best strategy. For a woman without any family history, and who doesn’t have the established risk factors, do we follow the same plan?”
More Expensive Sequencing Would Be Needed
Dr King and colleagues supported their call for universal testing with results of a study that was conducted among an Ashkenazi Jewish population in Israel. Within this cohort, 11% of breast cancers and 40% of ovarian cancers are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2.
But that population is quite different from that in the United States, explained Kristen Mahoney Shannon, MS, CGC, director, Cancer Center Genetics Program at Massachusetts General Hospital in Boston, and a member of the panel that developed the “Genetic/Familial High-Risk Assessment: Breast and Ovarian” guidelines from the NCCN.
“There are three mutations in two genes: two specific ones in the BRCA1 gene and one in the BRCA2 gene, that are common in that population,” she said. “Those are the founder mutations, but there are no real founder mutations in the general population of the United States because of the complicated genetic mix.”
Thus, in order to do widespread screening in the United States, it would be necessary to look at the two genes in their entirety,” Shannon said. “You just couldn’t look for founder mutations.”
A woman living in the United States would need to undergo full sequencing, and that comes with a higher price tag. “It would be much more expensive, running about $4000 a test,” she said. “Just testing for founder genes would be far less expensive.”
For Ashkenazi Jews living in the United States, they might be able to test for founder genes, but it would depend on the possible genetic mixing in their family, she noted.
The Trouble With Variants
One of the other main issues of universal testing is figuring out what to do about results that are less defined. In some populations, a wide spectrum of different mutations in both genes is present. Currently, about 4% of women will end up with an ambiguous “variant of unknown significance” (VUS), and for right now, it is unclear what these variants may mean. In a population with a low prevalence, and outside the setting of a significant family history, they can be even more difficult to interpret, explained Haidle.
“We may end up overtreating women, because the management guidelines that exist now were developed in the setting of women who had family histories,” she said.
A VUS result will also create more downstream costs, as some women will undoubtedly select more aggressive follow-up. “If those patients opt for surgery, such as a prophylactic mastectomy, the cost would be about $50,000 per patient,” said Dr Finley. “If half of the VUS population, or 1.7 million patients, undergo such a procedure, the cost would be about $85 billion.”
Some VUS patients will choose to have an annual MRI instead of surgery, and if the same number were screened at a cost of $1000 per MRI each year for 30 years, that would total about $51 billion, he added.
If testing is opened up to the general population, the 4% incidence of VUS will also be higher, which in turn could lead to them being misinterpreted, and with the potential to cause real anxiety and harm.
But the question of universal testing does lend itself to a broader argument—why stop at BRCA? “Why not just do a whole slew of cancer predisposition tests,” Shannon pointed out, “when we have effective treatments?”
Lynch syndrome, for example, has roughly the same prevalence as BRCA mutations in a general US population and accounts for about 2%-3% of all colon cancer cases and 2% of endometrial cancers. “We have very effective screening and prevention tools for Lynch syndrome,” said Shannon, “So if we test for BRCA, then theoretically we should be testing everyone for this one as well.”
And universal testing for all of these hereditary cancers would be extremely costly, Shannon added.