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.
5 responses to “Questions For The Panel”
I have a few thoughts about this.
1. I think your thought of these professional organizations keeping tabs on the “appropriate” genes for cancer panels might be a good idea in theory, but in the current trend of genetics it doesn’t make much sense. How often would they update these recommendations? Only on a regular schedule, or every time a new and relevant paper is published that makes a new gene a good candidate for inclusion on these panels? Quite often the lab will know that this paper is coming, and is ready to offer testing very soon after. Should it not be available to patients then as an “approved gene”, because NSGC doesn’t have time to evaluate it yet? And dare I ask…who would be on these committees?
2. Your idea of “justifying” extra genes not approved by such committee, again, sounds like a good one. But remember that the technology used by most labs does not allow for singling out particular genes for inclusion/exclusion in sequencing and analysis. So what good would that information be, if you still are required to test for the entire panel of genes?
3. You only briefly mention cost, which I think is a much bigger deal to most patients than you are letting on. Does it really make more sense to not send to lab X because they have one extra gene, when lab X can offer the test to the patient at no out of pocket charge, vs lab Y that would be thousands of dollars?
4. I think it’s fair to ask the lab to share whatever information they know about the genes on their panels, but asking them to provide a “balanced discussion” seems a bit extreme. I hope I don’t sound offensive in saying, that’s your job as the clinician. Why ask the lab to do it? You have access to the same literature they do, get in there and look up this information, and form your own opinions. In my experience, they’re always willing to discuss different opinions with people who have educated themselves.
This topic isn’t only for cancer, genetic testing in panels is now available and useful for a variety of conditions, and will only grow with time. So thank you for opening up this discussion, I’ll be interested to see how this turns out.
Well, Sarah, I don’t know if you work at a lab, but if not, you are doing a great impression of such a person! 🙂
You wrote: ” I think it’s fair to ask the lab to share whatever information they know about the genes on their panels, but asking them to provide a “balanced discussion” seems a bit extreme. I hope I don’t sound offensive in saying, that’s your job as the clinician.”
Well, yes, Sarah, I actually do find what you say a bit offensive. Or defensive. Asking the lab to provide a balanced discussion, or at least an up-to-date rationale for their products, is appropriate. Gives clinicians a better idea what is truly driving the lab and how they think.
You wrote: “Why ask the lab to do it?”
Well, the lab is the entity determining which genes it has deemed worthy of testing, and in what combinations. Who better than the lab that made these decisions to explain the pros and cons and basis of their decision making? I can’t speak for them. Or read their minds.
You wrote: “You have access to the same literature they do, get in there and look up this information, and form your own opinions.”
Wait…maybe you are a professor who works at a genetics lab? Or a researcher? A full-time practicing clinician? I don’t think so.
You wrote: “In my experience, they’re always willing to discuss different opinions with people who have educated themselves.”
Your experience has been vastly different from mine. I find the level of inflexibility and attitudes of superiority quite frustrating, actually. I’d just like to hear the labs explain their positions and rationale, minus the sound-bites.
I do see Sarah’s points and agree with the difficulties she cited. However, I am hoping there can be some collaborative work between labs and professional organizations in an effort to shape how testing will evolve instead of a “here is the latest and greatest” approach. I am very concerned about what will happen when our only choice is a panel and, then, when our only choice is the whole exome. Many of my patients do not want all of that information not to mention how complicated sessions will become. But, it seems this is on the horizon as one lab is planning to offer a 25 gene panel and that’s it. It seems as our choices increase they are also dwindling.
So, the cost effectiveness of these panels doesn’t always hold water. I work with payers developing ind implementing policies for genetic testing and have seen insurance companies billed for each 2013 CPT code associated with theses panels I.e. They bill for BRCA, all of the LS genes, p53, PTEN and misc lab codes for the genes that don’t have specific codes. When all of theses codes are added up the payer can get a bill for close to 70K! It is unclear how much they actually paid the company, but the point is we can’t necessarially make the argument that testingt his way will save healthcare dollars.
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