Tory Galloway thought her negative result on a widely-used test sold by Utah-based Myriad Genetics Inc. cleared her DNA as a cause for her fallopian tube cancer.
She happily advised her four sisters that the disease didn’t result from a family trait. The relief from the December 2010 test, though, was short lived. In October, after getting results from a broader scan at the University of Washington that included dozens of genes, she learned the truth: Her cancer was caused by a mutation that wasn’t included in the Myriad product.
“It makes me nuts to even think about it,” said Galloway, a landscape designer in Indianola, Wash.
The broader test, created by University of Washington researchers, uses technology to identify as many cancer risks as possible. There’s one problem: Such a test can’t include the BRCA1 and BRCA2 genes that are the most common inherited causes for breast and ovarian cancer because Myriad owns the patents on them. This prevents other U.S. laboratories from using them in a commercial test.
In the mid-1990s, Myriad helped kick-start the gene-testing revolution by pinpointing the two BRCA genes. Now, the world’s biggest genetic testing company for breast cancer, with a market value of $2.2 billion, is under attack by researchers, genetic counselors, doctors, and their patients.
Besides stifling competitors from offering combination tests, including the BRCA genes, critics also said the company won’t share data from decades of testing that could aid research into how best to interpret screening. They said Myriad doesn’t adequately respond when other researchers find added BRCA mutations that address risks their current tests don’t cover.
“What is at stake is the way we want our health-care system to work,” said Robert Cook-Deegan, a professor of public policy, biology, and medicine at Duke University in Durham, North Carolina, who supports limits on gene patents. “The testing has been set up by Myriad to optimize this business model. It is not set up to optimize public health outcomes.”
The dispute, which has grown in intensity as more and more cancer-causing mutations are found, has spilled out of the laboratories and clinics into the U.S. Supreme Court. A ruling next year in a case challenging Myriad’s hold on the BRCA patents could either support the company’s profit-driven motives or redefine a nascent industry in a way that affects millions of dollars in revenue.
Myriad officials reject the criticisms, saying they offer faster, more accurate testing for harmful mutations in breast cancer genes than any other laboratory in the world, and that its patents haven’t hindered research or patient care.
“Myriad has never done anything to harm patients,” CEO Peter Meldrum said during an interview at his company’s headquarters in Salt Lake City. “We have the most accurate results, we give the fastest results.” There has never been a reported case in which Myriad wrongly told that a woman she had a cancer-causing mutation, he said.
Carol Mackoff, 70, a Chicago-based managing director for Rice Financial Products Co., says Myriad “saved my life.”
Mackoff tested positive on a Myriad test for a BRCA1 mutation in 2002 after visiting an ovarian cancer prevention program at Northwestern Memorial Hospital in Chicago, she said in a telephone interview. Within weeks, she had her ovaries removed to prevent ovarian cancer, and later in 2009 had a prophylactic double mastectomy.
Without the Myriad test, “I would have had cancer,” she said. “The fact that they developed these tests and gave me a tool to work with to allow me to prevent getting cancer, I owe them everything.”
Faster, cheaper DNA testing is revolutionizing medical care. Nowhere has the impact been felt more strongly than in breast cancer. A woman who tests positive using Myriad’s tests carries as much as an 80 percent chance that she will get breast cancer in her lifetime. Testing helps women take charge of their medical future, providing options that can include preventative surgery and more extensive monitoring.
Widespread use of the tests has made Myriad an unabashed financial success. The company’s testing business, led by its flagship $3,340 BRCA product, carries an 87 percent gross profit margin that in fiscal 2012 generated $496 million in sales, according to Myriad.
That’s helped boost the company’s shares 30 percent this year.
Meldrum and Utah researcher Mark Skolnick founded Myriad in May 1991, about a year after Mary-Claire King, a geneticist now at the University of Washington, stunned the scientific world by proving that a single gene can raise the risk of breast cancer. Skolnick is retired from the company.
Backed by venture capital money, Myriad beat King and her academic colleagues to pinpoint the location of the BRCA1 cancer gene and patent it. They won a similar race to find another gene linked to increased risk -- BRCA2. Myriad filed a patent application for that cancer gene just days before a British-led team published a scientific paper announcing they had found it.
Sales have soared, fueled by patents which give Myriad a virtual monopoly on genetic testing for hereditary breast cancer in the U.S. About 227,000 American women are diagnosed with breast cancer every year and about 5 to 10 percent carry the mutant genes.
“Nobody else has built a half a billion-dollar business around tests for single genes,” Peter Lawson, a New York based analyst for Mizuho Securities USA, said in a telephone interview. “They are the dominant player in the industry.”
Myriad is also “far and away the most conspicuous and controversial” testing company relying on gene patents, said Duke’s Cook-Deegan.
Although Myriad provides accurate testing for mutations in BRCA1 and BRCA2, its exclusive right to test those genes limits laboratories and researchers in developing new tests, said King, the University of Washington geneticist.
In 2006, after it became clear that Myriad’s main test missed some BRCA mutations, Myriad angered geneticists and genetic counselors when it didn’t modify its main test to include those mutations.
Instead, it came out with a separate test, now priced at $700, to detect the additional BRCA mutations missed by the main test. Insurance companies didn’t cover the second test for years, and most women didn’t get it until recently, genetic counselors said. Some women who tested negative on the main test may wrongly think they don’t have a cancer-causing gene.
Kathleen Maxian thought she wasn’t at high risk for inherited ovarian cancer, because her sister, who’d had breast cancer, had undergone Myriad’s main test and was cleared.
She was wrong. When Maxian developed ovarian cancer in 2009, she was shocked to find out that her sister had undergone only one of Myriad’s available tests. If her sister had gotten the second part of the two-part test, Maxian would have known that she was also vulnerable to ovarian cancer as well as breast cancer.
“It was absolutely devastating,” said Maxian, who said she would have gotten her ovaries removed and her cancer likely would have been prevented. “There are a lot of women out there like my sister and I ... we are time bombs.”
It is standard practice to split up tests, and insurers’ refusal to pay for the second test put Myriad in a no-win position, said Mark Capone, president of Myriad’s testing unit. The company has provided the second test free to patients who meet certain family and personal history criteria.
In 2010, King and her colleague, Tom Walsh, devised a new test that looks at dozens of breast and ovarian cancer genes, including the BRCA genes. When the University of Washington introduced a commercial version of the test this summer including 40 genes, it had to remove the BRCA genes because of Myriad’s patents, she said.
Use of the broader screens would eliminate delays and confusion caused by having to take as many as three rounds of tests that need to be passed by insurance, and may involve sending different blood samples to multiple labs, said Ellen Matloff, who heads cancer genetic counseling at Yale Cancer Center in New Haven, Conn., and is a plaintiff in the case.
“Every time a woman dies of breast or ovarian cancer who turns out to have a mutation in BRCA1 or BRCA2, or any of the 20 or so sister genes, I feel in a way that it’s on us,” King said in an interview. King is outgoing president of the American Society of Human Genetics, which has joined in amicus briefs with other organizations against gene patents. King recused herself from the discussions, she said.
Myriad is working actively on its own product to scan multiple cancer-risk genes at once, said CEO Meldrum. Although the new technology used for such tests is rapidly improving, it still is “not accurate enough now for clinical purposes,” potentially leading to errors if used before it is perfected, he said.
Myriad also refuses to share genetic data collected from many thousands of women tested since 2004, eight years after the BRCA test was first marketed.
Scientists worldwide are moving to place mutation data into public databases to improve interpretation of genetic tests and reduce the number of women left in limbo with ambiguous results, said James Evans, a geneticist at the University of North Carolina at Chapel Hill. Even in well-known genes, there are thousands of possible mutations in different ethnic groups, and it’s not always obvious whether a mutation is harmful.
In one effort, 48 U.S. companies and university genetics labs have agreed to work together to put mutations into a government-run database, said Heidi Rehm, a geneticist at Harvard Medical School in Cambridge, Massachusetts, who is heading the project. Myriad hasn’t yet agreed to participate, she said in an e-mail.
Myriad’s reasoning for the secrecy is straightforward. Sharing “doesn’t make a lot of business sense,” Meldrum said.
Myriad “is holding clinical testing back,” said Evans, a board member for the American College of Medical Genetics and Genomics, a plaintiff in the Supreme Court case against Myriad. “There’s no medical, or rational, logic here.”
Runi Limary, 36, of Austin, Texas, found a cancerous lump in her right breast in 2005 when she was 28. She had that breast removed, followed by 14 months of chemotherapy and antibody therapy. She put off getting Myriad’s test because her insurance didn’t cover it until she changed jobs in 2007.
The gene test was less helpful than she had hoped.
She had a mutation in BRCA1 that Myriad had only seen in two other patients, she said, which meant that the company wasn’t sure whether it was harmful or not.
As a result, Limary is in limbo. She faces an agonizing decision soon, whether to get her ovaries surgically removed to prevent ovarian cancer, she said.
If Myriad’s database was public, and if there were more competitors doing the test, she might have received a definitive answer sooner on whether her tumor was due to a bad gene, she said. She is a plaintiff in the patent case against Myriad.
There are simply too many questions left about genetic testing to allow Myriad to control results affecting millions of women, Limary said. “It is very disheartening,” she said.
Myriad is gearing up for what may be its biggest challenge -- defending its patents before the U.S. Supreme Court, which agreed on Nov. 30 to hear the case.
In that suit, the justices are being asked to decide whether BRCA or other human genes that have been removed from the body are products of nature, and thus ineligible for protection, or whether isolating and purifying the genes from the body creates a patentable invention.
The 20 plaintiffs include patients, scientists and genetic counselors, professional groups representing more than 100,000 pathologists, geneticists and lab workers, and the consumer health organizations Breast Cancer Action and Our Bodies Ourselves.
The plaintiffs won the first round in the case in March 2010, when a federal judge invalidated parts of seven patents. An appeals court partially overturned that decision this past August, setting the stage for the Supreme Court to take the case.
The high court is expected to decide the Myriad case by next summer.
If the patents are upheld, they will remain in force until 2015, Meldrum said. The company also has an additional 17 patents on its BRCA testing that, so far, are unaffected by that lawsuit. They provide strong protection until 2018, and by then Myriad will have introduced a new test that combines BRCA with the other cancer risk genes, he said.
“As a pioneer you will take arrows,” said Capone, the president of Myriad’s testing unit. “We have put the patient at the center of focus of the entire organization.”