Choosing a BRCA Genetic Testing Laboratory: A Patient-Centric and Ethical Call to Action for Clinicians and Payers

Genetic testing laboratories are using aggressive and manipulative tactics to capture market share in the BRCA testing market. Clinicians and payers are encouraged to utilize patient-centric criteria, including open access to data, to make decisions about genetic testing laboratories.The past 12 months in the world of cancer genetic counseling have been more notable, perhaps, than the past 12 years combined. In May 2013, Hollywood icon Angelina Jolie went public with her BRCA1+ status, thrusting the field of cancer genetic testing and counseling into the spotlight and increasing referral rates to clinics by as much as 40% (E. T. Matloff, MS, oral communication, July 2013).¹ One month later, the US Supreme Court unanimously ruled against the validity of patents that lay claim to genomic DNA in Association for Molecular Pathology v Myriad Genetics, Inc.² Within hours, multiple laboratories began offering more comprehensive genetic testing for the hereditary breast and ovarian cancer genes BRCA1 and BRCA2, and at half the cost. The battle for the multi-million-dollar BRCA testing market had begun.

This battle has resulted in some genetic counseling centers reporting that referring clinicians have begun to request, or demand, that their patients’ BRCA testing be sent to a particular laboratory. In several instances it was discovered that these clinicians were either paid consultants for such laboratories, or received speaking fees or research funding from those entities. This is clearly a conflict of interest in violation of a physician’s ethical obligations “to regard responsibility to the patient as paramount” and to discharge their “responsibility to participate in activities contributing to the improvement of the community and the betterment of public health.”³ Concerns about such manipulative tactics led us to develop a position statement stipulating that decisions about which genetic testing laboratories to use should focus on test quality, turnaround time, cost, and whether or not the laboratory shares its data in public databases (Table 1).

Without its patent-protected monopoly, Myriad now appears to be relying on trade secrets to maintain its share of the BRCA market.^4,5 The “trade secrets” are actually a database of BRCA variants of uncertain significance (VUS) derived from the thousands of patient tests they have performed over the past decade.⁵ The company once contributed its data to a public database maintained by the National Institutes of Health, but ceased doing so in 2004.⁴ Several Myriad scientists and executives have stated that the public variant databases are not properly curated and that contributing to such resources would cause more harm than good; however, by at least 1 account, Myriad disclosed that it made its decision to stop sharing data for the purpose of retaining data as a trade secret.^4,6

In Myriad’s Q3 Earnings Call Transcript of May 6, 2014, the company publicly acknowledged that in the context of PARP inhibitors, “Our competitors’ reliance on public databases with high VUS and error rates will further restrict patient access to this life-saving medicine.”⁷ The decision to hoard patient VUS data, even while recognizing that this decision will restrict patient access to lifesaving treatment, is incongruent with the American Medical Association’s (AMA’s) policy on Genome Analysis and Variant Identification (Table 2) and is considered unethical behavior according to the AMA’s Resolution E-9.095 on “the use of patents, trade secrets…or other means to limit the availability of medical procedures.”^8,9

Although variant classification is important, few BRCA tests result in a variant of uncertain significance (ie, 4.4% at Ambry Genetics¹⁰). Myriad itself reports a 3% overall variant rate, slightly lower than other labs’ and presumably attributable to the superior testing experience enabled by its patents.¹¹ Therefore, the vast majority of patients (~95%) are not impacted by a variant of uncertain significance, although the company describes its information as “vastly superior” and leverages variant classification ability as a major differentiator.⁵

Other laboratories offering BRCA testing have teamed with clinicians, scientists, and patients to expand the pool of publicly available genetic information for the betterment of clinical care and research as part of the Free the Data movement (http://www.free-the-data.org). This movement recognizes that patients, clinicians, scientists, and insurers could all benefit from pooling such information. It has gained traction in patient communities, and some patients now request that their genetic testing be sent to laboratories that share data. Many of these competing laboratories are advertising their data-sharing policies as a way to gain market share. As this movement progresses, creating public genetic databases that feature proper curation of data, transparency on how variant classification decisions are made, and open forums for discussion will be critical.

With the growing number of laboratories offering testing, insurers are beginning to contract with particular laboratories for BRCA testing, designating certain laboratories as their in-network providers.¹² Before negotiating such partnerships, payers and regulators have the opportunity to choose to partner only with high-quality laboratories that pledge to share all past, present, and future data in public databases. As Cook-Deegan et al write, “National health systems and insurers, regulators, researchers, providers, and patients all have a strong interest in ensuring broad access to information about the clinical significance of variants discovered through genetic testing.”³ This is particularly relevant for publicly funded insurers that could create incentives or make data sharing a stipulation for coverage.^4,13

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Our patients deserve for decisions regarding where their genetic testing is performed to be unbiased, free of conflict, and based upon considerations unrelated to the clinician’s self-interest. Moreover, sharing of genetic data will benefit patient care and clinical research, which may lead to lower healthcare costs for all moving forward. The choice to use only laboratories that are committed to quality, efficiency, and facilitating progress for all through sharing of data represents an important opportunity as our healthcare system evolves. Ellen T. Matloff and Rachel E. Barnett: Yale Cancer Genetic Counseling, Yale Cancer Center, Yale School of Medicine. Robert Nussbaum, MD: Division of Medical Genetics, University of California, San Francisco School of Medicine.References

1. Jolie A. My medical choice. The New York Times. http://www.nytimes.com/2013/05/14/opinion/my-medical-choice.html/?_r=0. Published May 14, 2013.

2. Supreme Court of the United States. Association for Molecular Pathology v Myriad Genetics, 2013 WL 2631062 (June 13, 2013).

3. American Medical Association. Principles of medical ethics. http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/codemedical-ethics/principles-medical-ethics.page. Accessed May 7, 2014.

4. Cook-Deegan R, Conley JM, Evans JP, Vorhaus D. The next controversy in genetic testing:clinical data as trade secrets. Eur J Hum Genet. 2013;21:585-588.

5. Pollack A. Despite gene patent victory, Myriad Genetics faces challenges. The New York Times. http://www.nytimes.com/2011/08/25/business/despite-gene-patent-victory-myriad-geneticsfaces-challenges.html?pagewanted=all&_r=0. Published August 24, 2011.

6. Ray T. In tackling the VUS challenge, are public databases the solution or a liability for labs? Pharmacogenomics Reporter. http://www.genomeweb.com/clinical-genomics/tackling-vuschallenge-are-public-databases-solution-or-liabilitylabs. Published February 12, 2014. Accessed February 27, 2014.

7. Seeking Alpha. Myriad Genetics’ (MYGN) CEO Peter Meldrum on Q3 2014 Results - Earnings Call Transcript. http://seekingalpha.com/article/2196503-myriad-genetics-mygn-ceopeter-meldrum-on-q3-2014-results-earningscall-transcript?page=3. Published May 6, 2014. Accessed May 7, 2014.

8. American Medical Association. D-460.971 Genome analysis and variant identification policy statement. www.ama-assn.org. Published June 2013. Accessed May 2, 2014.

9. American Medical Association. Amendment to Opinion E-9.095 Trademarks, patents, copyrights, and other legal restrictions on medical procedures.www.ama.assn.org. Published November 2007. Accessed May 6, 2014.

10. Ambry Genetics. BRCA 1/2 Test Information Fact Sheet. http://www.ambrygen.com/tests/brca1-and-brca2. Accessed May 6, 2014.

11. Eggington JM, Burbidge L, Copeland K, et al. Current variant of uncertain significance rates in BRCA1, BRCA2, and Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) testing. Poster presented at the European Society of Human Genetics (ESHG) Congress 2012.

12. National Society of Genetic Counselors. Cancer Special Interest Group listserv postings. www.nsgc.org. May 2 and May 5, 2014.

13. News Briefs. Genetics in Medicine. 2014; 16(5):357-358.

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