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Universal BRCA testing might not be worth the cost
Universal BRCA1/2 testing may not be cost-effective due to the rarity of these mutations and cost of testing, according to a viewpoint published in JAMA Oncology.
“The cost of BRCA testing would need to drop by 90 percent to be cost-effective for the whole population,” Patricia A. Ganz, MD, director of the division of cancer prevention and control research at UCLA Jonsson Comprehensive Cancer Center, said in a press release.
Patricia A. Ganz
The U.S. Preventive Services Task Force recommends BRCA testing only for women with a known family history of breast, ovarian, tubal or peritoneal cancers. However, Mary-Claire King, PhD, and colleagues published a viewpoint in 2014 in JAMA that supported routine population-based screening for BRCA1/2 mutations (King MC, et al. JAMA. 2014;10.1001/jama.2014.12483.).
In response to that viewpoint, Ganz and Elisa Long, PhD, assistant professor at UCLA Anderson School of Management, used decision-analytic modeling to estimate the cost-effectiveness of universal BRCA testing of all women in the U.S. aged older than 30 years, as well as the potential number of cancers prevented and life-years saved.
“[We] were really challenged to think about how it might be possible to implement universal BRCA1/2 screening at a population level when [it was] first proposed last year,” Ganz told HemOnc Today. “Although there is great appeal in identifying those young women who are mutation carriers where there is no known family history, it is a bit like looking for a needle in a haystack.”
Ganz and Long assumed one in 400 women carry a BRCA mutation.
Results of their analyses showed the cost-effectiveness of universal screening with Myriad’s test — which costs approximately $4,000 — exceeds $1.7 million per quality-adjusted life-year (QALY) gained compared with only testing women with a family history of breast cancer. Ambry Genetics’ test had a cost-effectiveness ratio of more than $900,000 per QALY gained.
Further, for every 10,000 women screened, universal BRCA screening compared with family history-based testing would avert only two cases of ovarian cancer and four cases of breast cancer and extend life expectancy by 2.1 days.
For 99.8% of women screened, a negative genetic test offered no gain in life expectancy, would not eliminate the need for regular mammograms and may even provide false assurance that a woman is not at risk for breast cancer.
“The unintended consequences of a negative test result — ‘you do not carry a serious risk for having breast cancer’ — does not take away the usual risk that 80% of the population of women have over their lifetime,” Ganz said. “Many women from ethnic minority groups would likely have mutation variants of uncertain significance, and explaining this is a nightmare even to very sophisticated individuals. It also requires investment in pre-test counseling, which would not likely be the case with universal screening.”
In comparison, genetic screening for a cohort of Ashkenazi Jewish women — who have a 1-in-50 ratio of harboring a BRCA mutation — would avert approximately 34 ovarian cancer cases and 63 breast cancer cases per 10,000 tested women. Life expectancy gains were 16 times higher than universal screening.
“The cost-effectiveness calculations clearly show that this is not feasible except for special populations in whom the mutation rate is high — like the Ashkenazi Jewish individuals,” Ganz said. “Reducing the price of testing, in which high laboratory quality is maintained, will be the only way that this can possibly occur. Maybe this will be the case in a few years.”
Ganz and Long also calculated the cost-effectiveness of other diagnostic techniques for breast cancer. They found annual mammography for BRCA carriers costs less than $30,000 per QALY gained, augmenting mammography with MRI costs less than $180,000 QALY gained and biennial mammograms for women aged 40 to 49 years with high breast density costs $75,000 to $89,000 per QALY gained.
Even under the assumption that risk-reducing surgery completely eliminates cancer risk for women identified with a BRCA mutation, universal screening still exceeds $970,000 per QALY gained compared with family history-based screening. If BRCA genetic testing falls below $250, a price indicated by Color Genomics, cost-effectiveness would improve to $53,000 per QALY gained.
“If only one in 400 women across the country have one or both of the BRCA1 or BRCA2 mutations, universal screening would cost $1 million to $2 million to detect a single BRCA mutation, or nearly $400 billion to screen all women in the U.S,” Long said in a press release. “Perhaps this money could be better spent on other diagnostic tools for young women, such as MRIs, to have the greatest impact.” – by Anthony SanFilippo
For more information:
Patricia A. Ganz, MD, can be reached at UCLA Jonsson Comprehensive Cancer Center, 8-684 Factor Building, Box 951781, Los Angeles CA 90095; email: pganz@mednet.ucla.edu
Disclosure: Long and Ganz report no relevant financial disclosures.
Perspective
Back to TopThe standard answer in the past has been, “Only if you have a personal or family history of cancer that suggests you might have a mutation present.”
As we learn more and more about BRCA, our response has gotten more nuanced: “If you have a family history of cancer — even a limited family structure — or a personal history of breast cancer especially at a young age, or triple-negative breast cancer, or high-grade serous tubal or ovarian cancer.”
But, after every attempt at a helpful response, we would conclude by saying, “Seeing a genetic counselor is the best way to understand your risk and decide if testing is appropriate for you.”
BRCA testing cannot be done like any routine blood test. The test requires deliberate thought and most importantly, education, both before and after.
When I, Dizon, was in Rhode Island, patients were typically referred to the high-risk clinic at Women and Infant’s Hospital in Providence, seen by a genetic counselor and had their cases reviewed at a multidisciplinary conference.
This ‘ideal’ is not possible in all clinics or geographies so it is imperative to train and educate specific providers to competently counsel within their health care communities.
Women must understand their personal risk for a mutation, what a negative test means and what the implications are of a positive test. Without true knowledge on this subject from the health care provider, women will be unsure of what to make of their own results or what steps need to be taken after finding a mutation.
Now comes a controversial call for universal BRCA mutation testing. Although we are keenly aware of the rationale that underpins this initiative, it gives us great pause because it assumes that testing is straightforward — either a cancer-predisposing mutation is present or it is absent. But it is not that simple — a negative test is not necessarily negative.
Now women also need to decide if they want “panel testing” to evaluate for potential mutations in other cancer predisposition genes. Lastly, with a positive BRCA mutation, decisions need to be thoughtfully considered, especially around the areas of family disclosure, screening and risk-reduction strategies, especially with regard to the role of prophylactic surgeries.
Beyond these practical considerations, Long and Ganz have identified the current inefficiency of universal BRCA testing — that it is not cost-effective. In their modeling, universal screening would exceed $1 million dollars per quality-adjusted year of life gained.
However, as genetic testing becomes less and less expensive, these tests — likely bundled as large panels — will become widely available and cost-effective.
We now need, therefore, to rigorously focus our medical school curriculum and continuing medical education on cancer and other genetic predisposition and interpretation of test results. Whether you are willingly waiting at the station or not … the train is coming.
– Robert D. Legare, MD, FACP
Women and Infant’s Hospital
Brown University
– Don S. Dizon, MD
Massachusetts General Hospital
Harvard Medical School