An Inside Look at Diagnostics
This case study illustrates the evolution of the diagnostic industry across different continents, diagnostic companies' evolving business models, stak...
It’s not often that a gene mutation becomes a topic for general discussion but the actress Angelina Jolie’s disclosure that she carries the ‘faulty gene’ that can lead to breast and ovarian cancer has raised the profile of BRCA testing. A US Supreme Court judgement means that Myriad Genetic Laboratories is no longer the sole provider of BRCA testing clinical services. Patrick Considine suggests that the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) should now play a leading role in ensuring the accuracy and precision of BRCA testing, as it has done previously for HER2 testing.
BRCA1 and BRCA2 are human genes that belong to a class of genes known as tumor suppressors. Mutation of these genes has been linked to hereditary breast and ovarian cancer. A woman’s risk of developing breast and/or ovarian cancer is greatly increased if she inherits a deleterious (harmful) BRCA1 or BRCA2 mutation. Men with these mutations also have an increased risk of breast cancer. Both men and women who have harmful BRCA1 or BRCA2 mutations may be at increased risk of other cancers. Current estimates are that about one in 1,000 women carry a BRCA mutation and that inheritance of BRCA mutations accounts for five to seven percent of all breast cancer.
To establish a person’s risk of developing breast or ovarian cancer a genetic test is carried out to check for BRCA1 and BRCA2 mutations. The clinical value of BRCA testing was headlined recently by the disclosure from actress Angelina Jolie in The New York Times: “I carry a ‘faulty’ gene, BRCA1, which sharply increases my risk of developing breast cancer and ovarian cancer.” Jolie, whose mother died of breast cancer, said she chose to have her breasts removed to reduce exposure. The high profile disclosure has led to unprecedented requests for BRCA genetic counselling and testing.
Until the Supreme Court judgement, Myriad Genetic Laboratories held the patent on the BRCA genes and was the only commercial laboratory in the US to test for BRCA mutations in the general population. The ruling is in part a victory for a group of scientists and patients’ rights advocates that argued Myriad’s patents chilled scientific research and hampered access to affordable genetic risk screening. The cost of Myriad’s BRACAnalysis test in the US varies somewhat by payer but is generally in the $3,000 to $4,000 range. Currently, BRACAnalysis testing accounts for a striking 88 per cent of the company’s nearly $400 million in annual revenues, with only 2 per cent of those sales occurring ex-US.
The judgement will allow the market to open up so that other laboratories can offer the test and that should make the test less expensive and more available to more women. Already a number of laboratories have signalled their intention to offer BRCA testing. Within hours of the decision, the University of Washington and Ambry Genetics said they would immediately offer expanded testing that included BRCA1 and BRCA2. Quest Diagnostics, one of the largest commercial laboratories in the US, announced “we now intend to validate and offer a BRCA1 and BRCA2 test service to physicians and patients later this year.” Others include DNATraits, part of Houston-based Gene By Gene, Ltd, which said it would offer BRCA gene testing in the United States for $995, less than a third of the current price.
Myriad, despite its critics, is considered as generally doing a good job by most physicians, with BRACAnalysis considered to be the best BRCA gene test on the market. Myriad has several competitive advantages based on its long experience in BRCA testing. It runs a highly efficient laboratory, has developed a network of health professionals who use its services, has secured agreements with hundreds of payers, has brand recognition based in part on direct-to-consumer advertising, and has a trained sales force.
However, Myriad’s proprietary Variants of Uncertain Significance (VUS) database, which records rarely-occurring mutations within the BRCA gene and reduces the number of uncertain test results, may give Myriad a strong competitive edge. Myriad has amassed its database of thousands of sequences of the two genes and correlated mutations in these sequences with risk-estimate indicators based in part on the medical histories of the patient and her family members. At first, the company freely shared this information by contributing it to public databases that researchers and clinicians could access. But in 2004, Myriad stopped these contributions, saying the potential was too great that the Myriad sequences were being used to generate inaccurate risk estimates for patient.
The key driver of demand for an alternative to the BRACAnalysis test will be determined by whether Myriad allows public access to its database. “While some US physicians have shown interest in reconstructing their own Myriad VUS databases from patient reports, this fragmentary effort would likely take a long time. The Supreme Court’s decision therefore seems unlikely to change the status of Myriad’s BRACAnalysis as the test of choice for hereditary breast cancer gene testing in the US, thanks to this VUS database,” says Dr. Thompson (GlobalData’s senior analyst covering in vitro diagnostics).
Myriad customers have joined forces with geneticist Robert Nussbaum, MD, of UCSF, to do an end-run around the company’s vast database. In Nussbaum’s Sharing Clinical Reports Project, clinicians and patients around the country are encouraged to submit the reports generated by Myriad for each patient. The reports contain valuable information about mutations and risk estimates. Alone, each report is useful only to the patient for whom it was generated. But if enough patients and researchers were to submit the results, the project could begin to reconstitute the database Myriad now keeps under lock and key. Nussbaum estimates that within a year researchers will have access to enough high-quality data to render Myriad’s head start unimportant. Stanford big-data expert Atul Butte, agrees that the landscape for genetic diagnostic testing is likely to change rapidly as a result of this week’s events. “I think the community is eventually going to end up with a resource that’s even better than what Myriad has. Myriad may know better than anyone else what the natural variation is in these genes. But the true value lies not just in knowing what the variants are, but how they connect to clinical disease. If the research and clinical community do this right it will be able to connect the sequences directly with patient outcome and generate more-meaningful results.”
Now that a number of laboratories will be providing BRCA testing clinical services, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) should play a leading role in ensuring the accuracy and precision of BRCA testing through the development of guidelines, recommendations and a proficiency testing program as they have done for breast cancer HER2 testing.