Women who are carriers of mutated BRCA genes are known to have a significantly higher risk for developing breast and ovarian cancers than those who don't have the mutations. But a new study by UCLA faculty questions the value of screening for the genetic mutations in the general population—including those who do not have cancer or have no family history of the disease—because of the high cost.
The UCLA researchers found that compared with universal screening, other diagnostic tools remain more efficient and might be more cost-effective.
The viewpoint was authored by Dr. Patricia Ganz, director of the division of cancer prevention and control research at UCLA's Jonsson Comprehensive Cancer Center, and Dr. Elisa Long, assistant professor at the UCLA Anderson School of Management.
The researchers concluded the BRCA genetic test that is most widely used today—marketed by Myriad Genetics; it sells for about $4,000—is too expensive to warrant universal screening, given how rare BRCA mutations are in women.
"The cost of BRCA testing would need to drop by 90 percent for testing to be cost-effective for the whole population," Ganz said.
Long and Ganz calculated that for every 10,000 women screened, BRCA screening could avert four cases of breast cancer and two cases of ovarian cancer more than family history-based testing. But the BRCA screening would only extend patients' life by an average of two days. For 99.75 percent of women screened, a negative genetic test offers no increase in life expectancy, nor would it eliminate the need for regular mammograms, and it could provide false reassurance that a woman is not at risk for breast cancer.
The findings build upon previous work by other researchers that analyzed genetic screening of women of Ashkenazi Jewish descent, a population in which one out of every 50 women carries a harmful mutation. Because a larger percentage of this group were identified as BRCA mutation carriers, Long and Ganz found that the approach would yield an estimated 62 breast and 34 ovarian cancers averted per 10,000 women tested, and gains in life expectancy that were 16 times higher than with universal screening.
Of the 233,000 breast cancers diagnosed annually in the United States, only 5 to 10 percent are attributable to mutations in the BRCA genes. Women with breast cancer who carry these mutated genes usually develop the disease at a younger age, often in both breasts, and the cancer is often a more aggressive sub-type such as triple-negative breast cancer.
Harmful BRCA gene mutations are more likely to be found in families affected by breast and ovarian cancers, and carriers can pass the mutated genes to both daughters and sons. Those who carry a BRCA mutation are thought to have a 45 to 80 percent lifetime risk of developing breast cancer. Women carrying the BRCA-1 mutation have up to a 39 percent lifetime risk; women with BRCA-2 have a 10 to 17 percent lifetime risk for ovarian cancer.
The U.S. Preventive Services Task Force advises BRCA genetic testing only for women with a known family history of breast, ovarian, tubal or peritoneal cancer.
Long said that although the Myriad test remains the most commonly used test for BRCA mutations, a new $249 test recently announced by Color Genomics could encourage other companies to introduce lower-cost genetic tests—which could make universal screening more practical and more affordable. She noted, however, that questions would remain about the feasibility of providing personalized genetic counseling services on such a large scale.
"It's like looking for a needle in a haystack," Long said. "If only 1 in 400 women across the country have one or both of the BRCA-1 or BRCA-2 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 United States. Perhaps this money could be better spent on other diagnostic tools for young women, such as MRIs, to have the greatest impact."
Long has a personal connection to the BRCA-1 mutation. She herself is a carrier, and last year, at just 33 years of age, she was diagnosed with triple-negative breast cancer, the most aggressive form of the disease. She had no family history of breast cancer.
Her treatment consisted of six rounds of chemotherapy, a bilateral mastectomy and reconstructive breast surgery. Fortunately, the chemotherapy killed the cancer before her first surgery, increasing her five-year survival probability from 60 to 95 percent. In July, Long also had her ovaries and fallopian tubes removed, which reduced her risk of ovarian cancer to less than 5 percent.
"On a personal level, I would have benefitted tremendously from universal BRCA testing, because I had no family history of breast cancer," Long said. "But as a health services researcher I must also consider the relative value of different medical interventions. Many patients wish to know more about their genetic risk factors, and as more firms begin to offer genetic testing, we should expect the price to decrease, eventually making this an affordable policy."
The study will be published online by JAMA Oncology on September 3.
UCLA's Jonsson Comprehensive Cancer Center