If you are a genetic counselor engaged in testing for hereditary cancers, I suspect you are as bewildered as I am these days. With so many labs offering BRCA testing post Association for Molecular Pathology v. Myriad Genetics, Inc. it is difficult to know which labs best serve our patients in terms of value, reliability, insurance coverage services, clinical support, and quality assurance. Familiar labs are offering new tests and unfamiliar labs are offering testing at Costco prices. Not to mention various law suits and counter-suits over BRCA testing that make me worry that some judge somewhere is going to tell a lab to put all of its testing on hold, leaving patients’ test results in legal limbo.
But what really has me confused – and not a little bit upset – are the new multi-gene cancer panels.
The advantages of the multi-gene panels are obvious. They are cost-effective. They help avoid pondering “Gee, that family really could have been a Cowden. I really should have run PTEN” into the sleep-disturbed wee hours of the morning. Panels will also probably result in significant syndromology reassessment. If you offer PTEN testing only to families who look like they have Cowden syndrome, you lose much of the true clinical variability of the condition. And, with all respect and apologies to Robb Pilarski, Cowden syndrome is in serious need of re-assessment.
Savvy patients are beginning to demand multi-gene panels because they read about them on the Internet or heard about it at their support groups. And I would not be at all surprised if DTC marketing of gene panels starts to rear its ugly head along side the tadalafil, cyclosporine, ibandronate, and eszopiclone commercials that run during the evening news.
So what’s not to like about multi-gene panels? Let’s face it – many of us are just plain bored with BRCA testing. Panels all cost about the same price, and not terribly more expensive than just running BRCA1/2. Woe to a clinic that only offers BRCA1/2 testing when their crosstown rival routinely offers multi-gene panels to everyone. And who wants to look like an out-of-it fuddy dud who only offers a test developed in the previous century? Isn’t it great to have a choice to run a 6 gene panel, a 16 gene panel, a 26 gene panel, or a 49 gene panel to suit the needs of patients and clinicians? You just choose the panel that’s right for the patient.
And therein lies the rub. How do I know which panel is right for my patient? Labs offer little in the way of clarification as to why certain genes are included or excluded from a panel. From the clinician’s perspective, it seems like the choices reflect the arbitrary expertise of the lab with certain genes, the economic calculations of a given lab, and the desire to out-gun the other labs – why sail a 6 gun sloop when a 40 gun ship of the line can blow it out of the water? In my darker moments, I think that we sometimes choose a lab because a famous geneticist is affiliated with it or a friend from grad school works there.
If clinicians and the labs are honest about it, most of us have little idea of how to guide patients who have a deleterious mutation in genes like RAD51, GEN1, XRCC2. Sure, most labs provide references that might justify inclusion in the panel. But the labs do not cite contrary articles that suggest the predictive power of the particular gene might be low nor do they mention the paucity of publications on the clinical management implications of many of the genes.
There is also a noticeable absence of information on the demographic, clinical, or family history characteristics that might point to one panel over another. Are mutations in one set of genes more common in Russians, Japanese, or Native Americans? Are weak family histories suggestive of one group of genes and strong family histories indicative of another set of genes? What about age of onset? The tumor’s genetic or pathologic profile? Breast only families? Breast and colon families? Clinicians don’t know and neither do the labs.
A step in the right direction will be the pre-conference symposium on gene panels at the upcoming NSGC Annual Education Conference on October 9th. But that is only small bandage on a gushing artery. Bigger measures are needed, and here I offer a few:
1) The key professional organizations – NSGC, ASCO, SGO, etc. – need to form a joint committee that identifies a minimum set of critical genes that should be included on all breast, ovarian, or whatever cancer panels, à la newborn screening. Labs would be free to include whatever additional tests they would like. A joint panel would prevent each society from recommending its own preferred panel that might result in confusingly different recommendations from other professional organizations. Such a panel must take great pains to avoid any financial or intellectual biases.
2) The genes included on the panels should be rated according to their clinical utility and the strength of the data based on an analysis of peer-reviewed publications.
3) Centralized databases should be established for tracking patient outcomes, clinical and demographic variables, and variants of uncertain significance. Labs that fail to participate in joint databases should be singled out so that clinicians would have the option not to utilize labs that declined to participate in joint registries. While it is important for labs to stay competitive, fiscally sound, and profitable, we can’t lose sight of the core ethical value that the primary goal of genetic testing is to serve patients, not bottom lines. Failure to share data strangles the tree of patient care at its roots.
4) Lab websites should include a balanced discussion of the pros and cons of why each gene is included in the panel – particularly for those genes that are not recommended by the above suggested joint committee – and a regularly updated link to a Pubmed search for that particular gene, not a simple link to one or two articles.
5) The joint committee could also serve an advisory and educational role to health insurers so that patients have equal access to appropriate testing, regardless of which plans cover them.
No doubt The DNA Exchange’s wise and insightful readership have their own ideas, opinions, and recommendations. Let’s hear about them.