PNR Rendezvous - Genetic Testing in the Era of Genomic Sequencing - 08/15/18
All. Right we're recording now. Hello. Everyone, I'm Carolyn, Martin I'm going to be your host for today's PNR, rendezvous, session, you've. All probably noticed, Hadj necks is becoming more a part of our healthcare in recent years tonight. Testing, whether through a healthcare provider for, a direct-to-consumer, kit. Is all, very complex, and is all very complex, perplexing. It is, a fascinating, topic and today's, presenter, will shed a little bit more light about this for, us in just a bit but first I would like to review some of our housekeeping, tips as, you've probably noticed you. Were muted as you enter the session, today and you, will not be able to unmute yourselves, but, during, the session, you're free to type. In the chat box your questions and comments and towards. The end of the session if. We have time there will be an opportunity for you to also verbally, ask your questions and, as. You use the chat box please make sure it says is going out to all participants. So that everyone, can see your questions, and comments and if. You would like to use the closed captioning, the link is there on the screen for you to use. We. Would appreciate it if you would take some time now to fill out a survey for us the link is there in the chat box it's. Just a couple of questions we just like to see who we reach in each of our webinar. Sessions, and I'll, give you a little bit of time here to go ahead and so that out. And. For, attending, today's, pin our rendezvous either. Live or via the recording, you can get an MLA C e credit. And if you would like to receive this credit please, stay on the webinar and at the end we will provide you with some more information for, that also. Keep in mind that whether you want the CEO or not we would appreciate you taking the time to fill the survey we. Take these comments, very. Seriously. And we would appreciate, having. You fill that out. Now. I'd like to introduce today's, presenter, Laura. Amendola, is a licensed, genetic, counselor as well as a clinical associate professor here at the University, of Washington's, division, of medical, genetics and so.
We're Very happy to have her here today so Laura, we're, looking forward to your presentation, and I'll turn it over to you now, great. Thanks so much Carolyn, I'm I. Think, we're going to start actually with a poll, question um yeah. I'll let's get, to the next page and I'll open that up. Great. So I wanted. To start with a general question, to. Explore. Interest. In genetic. Testing in, this community, of folks for this webinar today. So. If you could respond. Either yes or no to. The question have you ever considered having, a genetic, test and. It's. There in the poll rather. Than responding. Through the chat. Looks. Like the responses, are rolling in, great. All, right I'm going to close the poll. Ask. The great love about 20, more seconds to respond, and. Almost. There okay. There. You go. Okay. So. It looks like okay. So more. People have considered, a genetic test than haven't, great. Yeah so I think one of the things we're going to talk about today, is, increasing. Access to, genetic testing and knowledge of genetic, testing in the community. And. I think it is something that people are thinking about more and. Trying to get, information on, so yeah. That seems reflective. Of maybe ten years ago people would would. Be more likely to respond know that, it's not something they had ever heard of or thought about for themselves okay, well, thanks for saying that all. Right all right. Okay. Great. And I'm going, to. Do. This. Okay. Okay. Can you see my screen okay. Yeah. Looks good great. All right wonderful so yeah, as Carolyn, said I'm a gender, counselor at the University, of Washington. I've. Been here for, almost, seven. Years now. And I've been at a genetic, counselor. For. Almost, ten I, worked. In clinical, genetics for a while and then I've been doing researcher, at the University, of Washington, for. Yeah. Most of my most of my time, so. I'm going to talk, today about. Who. Genetic, counselors are and what genetic counseling, is I, think it can be an abstract idea, so. Hopefully, as we go through, some. Of the examples and, talk through, what's. Unique about genetic, testing and how genetic. Testing has changed, that will maybe. Become a little more clear. And then touch on some of the changes in genetic testings, over, the last five or ten years with the example, of breast. Cancer that runs in families and, then, at the end talked about some, of the research that's been done and that I've been working on with, bringing.
New. Genetic, tests exome. And genome tests, into. Clinical, genetics. So. This is a word, cloud when, you, look. Up genetic, counseling, you. Can see some, of the. Words that might be associated with, that. Like. Client, information, knowledge. Clinical. And. When we think about where. What. The background is for genetic counselors, we are health professionals, we have graduate, degrees. It's a Masters, of Science degree, in genetic, counseling we, have, done courses in psychology counseling, and genetics, and done, clinical, rotations. And a variety of different specialties, we're, also nationally certified and, then there's licensure, in in some states, so we're allied, health professionals. And. A lot of times we work with medical. Providers. Physicians. Who are specialized, in genetics, or, the. Other kind of, disease areas where we're genetic counselors practice, there's, also an. Accreditation. Council for genetic, counseling and there's currently 39 programs, in the United States and four in Canada, and there are others I'm internationally. As well but. These are the ones that are accredited by the. North. American body and when, I looked up this number there I think we're about thirty on my slide from three, years ago so it's really the, number of programs is expanding. To meet the needs of genetic, counselors. So. What do candidate, counselors, do. When. I say I'm a genetic counselor people. Sometimes ask about designer, babies, that, is not something that we do. We. Also don't. Do. Lifestyle. Or recreational. Genetics, so it's. Not. A clinical. Genetic, issue to, try and find a genetic, way to lose, weight or your. Genetic way to match. With your true love. So. What is it genetic counseling, this, is a definition. From the National, Society of genetic counselors. From. 2005. Where. Genetic counseling is defined, as the process of helping people, understand. And adapt to the medical psychological. And familial. Implications. Of genetic contributions. To disease that's. Pretty high level, we'll. Go into a little, more detail. Typically. Genetic counselors, work in one, of three, areas, I. Would, say the majority still, probably work in genetics, clinics, and typically, they're specialized. In, an. Aged. Population. So adults. Or. Children and. Then, also there are disease specialties, too so there ISM can't. Specific cancer genetics, clinics or there, might be specific. Like. Down syndrome clinics. For. Children. Or a, clinic, for children born, with cleft lip and palate, so. Various specialties, and then of course M pregnant. Couples as well for prenatal genetic counseling. Jena counselors also practice in laboratories. Doing. Interpretation. Of genetic. Variation to see if gather. Evidence, them about. Whether that variation, is clinically meaningful and, they can also be liaisons, between laboratories. And providers, who order, genetic tests and then. Research. Is also I think a, minority. Of jak counselors are working primarily, in. Research, and like. For myself with. My role and that we do have a. Contribution. To. Conducting. Research. Projects, and then contributing, to the literature for. Genetic counseling in, clinical, genetics. So. The goals of genetic counseling there, are many but. One of the primary ones is to provide information to, families who have. A genetic condition condition. Themselves or may be at risk to inherit, a genetic condition so. The hope is they'll they'll walk away understanding. Information. And that that. Can help them to. Be. A participant when, making decisions about their, medical care and how that they want to manage any associated. Health problems. We. Also provide. Supportive, counseling to families, and serve as patient advocates we. Can be educators, and resource people for. Other health professionals. So. Non-genetic. Providers. And, also for the general public and then. As I mentioned contribute, to research that's related to genetics. One. Of the primary. Tenets. Of genetic counseling, is this idea of. Non-directive. Nough switch, is illustrated, in this quote. It. Is not the duty of the healthcare provider to offer direct. Advice to dictate the lives of others but to ensure that individuals have, the facts to enable them to make their own decisions.
So. One. Question that comes up, frequently. During genetic, counseling. Appointments. Is what, is a genetic, test. This. Is a definition. From. 2000. From. An oversight, committee for, genetic tests saying. That it's an analysis, done on DNA, RNA or chromosomes, to find heritable mutations, but. Usually we tell patients, that you know it's a blood test where we're looking at genes, and we try and explain. About changes. In those genes and what they may or may not mean. But. More importantly how our genetic, test difference, we try to be careful not to create a sense of them what we call genetic exceptionalism where. We, treat genetic different from other areas. Of healthcare but I think there are you, know a few ways that deciding. Whether or not to have a genetic test is, different than when, you go to the doctor with. You. Know a symptom, and then you have a, test, to see. If you can find the reason for that symptoms. So. One, difference, is that these, results could be used for medical management but also they, can be used for personal decision. Make so, for example if you find that you, have. A genetic disease that might impact. Your plans, for, having, a family or how you go about having, a family. Results. Often apply to other family. Members as well so, thinking about if you have. A genetic condition a lot of patients are concerned about the, possibility of passing that to their children that's a big motivator for having, genetic testing. So. Thinking about it in the context, of that entire, family. And. Then we also hope, that any, genetic, testing includes, an informed, consent conversation. An. Interpretation. Of that result. And what it means for the patient and then any follow-up, medical. Or psychosocial services. Coordinated. As needed. So. That it's more of a discussion. And. More. Of a. Communication. Between the provider and the patient. There's. Also some stigma, of, genetic. Disease or, carrier, status. There, is a law, it's abbreviated here, as Gina it's the genetic information non-discrimination. Act. It. Was passed around 2008. Where. There is protection for people with. Respect to employment. And, health, insurance, so you can't be fired from your job or, lose, your health insurance because you have genetic. Disease or predisposed. To develop, the. Symptoms of a genetic disease however, there's no protection for life insurance, long term care and disability, insurance so, that part, of the conversation that, we have with patients especially, when they're looking, at them, testing. For a condition, that may, manifest in the future, and then. Predictive. Testing as I just mentioned there's, a lot that we don't know, so again comparing this to getting, an. Explanation for, a symptom, that you have we. Think about absolutely, called penetrance in genetics, so that's whether. Or not you'll even get the disease few there, are few, diseases that 100%. If you have the gene mutation you, will get the disease a lot of them are either highly, penetrant, so like 80% chance, if you live to be a hundred you'll, show, features of that disease but some of them are like 30% or 40% and, that's. Uncertainties. That we, come. Out, of testing, with even when we get a positive result and then.
Another. Idea we, describe, as variable, expressions so this is okay you get the disease but, then how old are you and that happens are you 30 are you 40 are you 50 and. Then how bad is it and how, fast. Does it progress. So. A lot of uncertainty. So. Some questions to consider, for. People thinking. About genetic testing and for us as genetic counselors or how. Will this result, affect medical, management that is a big piece that insurance, is thinking about is. What, does this result going to mean for the patient's, care also. For the family, and the, chance that this could happen again, for example if if. A child is born that has a genetic condition. And, then you. Know how can this help inform, screening, we do. Knowing. About the risks for future things to happen in, a patient, also. What are the possible results, if we know about a condition in the family, and we know what the gene mutation or, changes, and we can get, a yes or no answer when we do testing, but. More often we're, kind of searching, and looking at one, or two or ten or 200, genes and, and then we can. Have. The possibility to find what we call variants of uncertain significance these are changes in genes where we, don't actually know what they mean they're different from, what. We would expect but maybe they mean nothing because most changes, don't, actually, affect, the. Risk. For disease in a person and that's. Impractical considerations. A big one and that one that actually becomes a topic of conversation in most genetic counseling sessions is the cost of testing, and. Whether insurance will excuse. Me cover that cost or the patient may. Have resources, to pay out-of-pocket, turnaround. Time, for. Some patients. They, might make treatment decisions. Based on the results, so if someone's pregnant that's a very time sensitive. Time. For them to, use that information, or if someone is thinking about, like. A cancer surgery, they, may make different choices, if, they know that their risks of having a second cancer are a lot. Higher and the. Type of sample, that's. Kind of a coordination, issue of whether someone's local and we have access to a blood draw versus. Saliva and. Then potential, for additional testing depending, on the results, I'm, going to talk more about, has. Sequential. Genetic, testing so looking at one gene if that's normal the next one if that's normal the next one's a little, bit later but. For. Many conditions that's still how things are done you kind of rule out the most likely. Condition. First and then move from there but that has some logistical, considerations for. People coming back in for visits and more blood draws. So. This slide is just to highlight, the. Growth in the, number. Of conditions. Where genetic testing is available, since. 1993, and I know this is kind of old and stops in 2012, but you can imagine that that curve, has continued, to grow, exponentially. Okay. So, the. Things you talk about the. Evolution. Of genetic. Testing so some of the changes that have gone. On for clinical, genetics in the last five or ten years and I'm going to use the example of hereditary. Breast cancer. So. This will really scratch the surface but. It's. It's kind of a example, of the technology and some of the things that we've been dealing, with. So. A brief. Introduction. To hereditary breast cancer, and about. Five to ten percent of breast cancers are thought to be hereditary so the vast majority are. Happening. By chance for, people at older, ages and, then there's a chunk, that is what we call familial, where we see, saying. Whew. Cancer more often, in a family than we would expect but it it is not clearly. Being passed from. Through. Generations. From parent to child because. Of a single gene change. That's. What hereditary, breast cancer. And most. Of it is caused, by gene changes or mutations in. Either the, brca1, or brca2, gene. You may have heard of those called the bracket genes. There's. Also an increase or ovarian cancer, for people who have mutations, in those genes and, when we look at a family history we.
Think Of, hereditary. Breast cancer when we see a few different things one, is what, we've defined as a young age at diagnosis. So that cutoff is less, than 50, for. A lot of, insurance. Criteria. And. Also in the field but, premenopausal. Breast cancer. Is. Also, considered. To know young age. Family. History of breast cancers, and multiple affected individuals, and multiple generations male, breast cancer because, it's so rare and then, Ashkenazi. Jewish ancestry, because there are certain, changes at gene changes in that. Population. That. Increase. The likelihood for. Breast cancer and they're more common in that population than, others. So. Why would we do genetic. Testing for hereditary, breast cancer. One. Of the main reasons, is that if we we, know about an increased, risk for cancer then we say there's something we can do about it we can do. Earlier. Screening, and more frequent screening, to. Hopefully, identify, breast, cancer earlier, when. It's more treatable and then, also there are surgical, options that. Can be discussed to help, prevent cancer and that. Falls into that second bullet of having. This information to influence, life planning, for example with, BRCA. Mutations. There's, an increased risk of ovarian cancer so they talk about removing. The ovaries when a woman's in their, 30s, or 40s so maybe that woman might think about if, they want to have children doing, so earlier, in life and. So. In the past genetic, testing for breast cancer and many, other conditions but for breast cancer was. Done gene by gene it, was actually only done in one laboratory. Before, June of 2013 you could only send the test to one lab called, myriad genetics, some. Folks are maybe familiar with that history, where. They would look at brca1 into and that was kind, of the go-to test, if you were suspicious. For other hereditary, breast cancer, conditions, and the, two genes here, the, first one you would expect to see some stomach, cancer in the family and the second one you would expect to expect, to see maybe some breast cancer or some, brain. Cancer, I'm sure blood cancer, so. You're specifically. Thinking. About other breast cancer conditions you could then, test one of those if that's normal then test the other one. Etc. So it was a long. Process and, then. A. New. Type of. Technology. Was developed called next-generation, sequencing. That's, definitely beyond the scope of this talk to describe the. Technical aspect, of that but basically it, became. A, similar amount of money to, look. Through the sequence of a, bunch, of genes as it is to look at the sequence of one genes and so it's the same to look at five genes and to look at 100 genes so. That really made it a practical, option especially. For, conditions, where. There's. What we call locus, heterogeneity so that just means it's. A condition, where a lot of different genes mutations. And a lot of different genes can, cause that condition, and cancer. And. Breast. Cancer specifically. As well as colon cancer. Are.
Some, Of the big players where, there's a lot of, genetic. Heterogeneity, there's a lot of different genes we look at or. Could be responsible, for someone having, hereditary. Breast cancer, when. You look at the cancer. Gene panel. So we call it a panel. Of genes when there's a bunch of different genes we look at at once. And it ranges, depending, on. The. Lab and, depending, on what. You are, suspicious for you, could test for five genes you could test to 40-plus, genes some. Of the, panel. Gene panels for other conditions. Like retinopathy. Conditions. There's, like 250. Genes on there so it's a, it's, a lot. Of, sequence. Information for, the same amount of money. So. This is an example from one of them the. Clinical. Commercial. Genetic laboratories, that. We. Use here and is in the United States called, Ambree genetics, so, these are like. Your menu of options when, you do breast cancer genetic, testing you can go, for just the brca1, and 2 you can do a little, panel with brca1 and 2 and then some more. Common. But. Quite, rare still but more common hereditary breast cancer conditions, that are better. Defined, or you. Can do BRCA, plus expanded. And add some more what. We call moderate. Risk genes so maybe the chance of breast cancer is. Like 30% versus. The, high risk would be like 80% or. You can do this big. Big big breast cancer panel of all genes that I've ever been associated with breast cancer, that. We know of and then the last option is, them in both labs to have an option like this is we. Call them pan cancer panels so like all. The genes that we know of and, defining. Though of is is a different thing like. What meets the threshold to go on this panel, but it's its genes associated with all types of cancer so there's colon cancer genes on here kidney cancer, of. Course breast cancer. Etc. So, that is the biggest, picture. And. So questions to think about with panel genetic testing or a little, bit different, so. Some of the advantages of. Looking. At a panel. It's definitely. Cost-effective. We're getting a lot of sequence information for. The. Same amount of money and. It can be efficient, as well. Also. We, might. Be, more likely to find the reasons for breast. Cancer in the family if, we're looking at all the genes that we know about instead. Of just the most likely candidates, but. Then there are some disadvantages. Or. Challenges, to way as well, when. We look at a lot of genes it's much more likely we're going to find a change in one of those genes that were not sure what it means one of those variants, of uncertain significance. And also since these panels include, jeans, where it's not, they're. Not as well, as established, there's not as many people with that disease it hasn't been studied as much sometimes. We could find a gene mutation but, we don't have very clear recommendations. About what to do about it maybe, we will in 10 or 20 years but we don't right now have. Like an evidence-based. Management. Recommendation. For that patient. We. Can also find, especially. If you do one of those larger, panels, with all the different cancer genes maybe you find a colon, cancer gene mutation, in your patient with breast cancer and, that's, challenging because it's you know we. Don't have any evidence that it's related, to the breast cancer in that patient. But. Are they also at, risk for, colon cancer and managing, that. Can. Be sticky. So. One. Of the options for patients who are thinking about cancer. Genetic testing right now is a company called color genomics. Maybe some of you have heard, of it I call, it like kind of direct-to-consumer. Testing. They, have options for, cancer. Testing as well as some cardiac, genetic, testing, they have a 30 gene panel that they, offer for 250, dollars and it's all, patient. Direct pay I. Also saw an advertisement actually, this morning that they offer their on offering. A sale right now for just brca1, and 2 for, 50 dollars instead. Of 150 which it normally is so. So, the idea is that this is a more accessible. Test. For, patients, whose insurance may not cover genetic.
Testing, And. The way it works is you you, can order this test for yourself. Online. And, have a fit kit mailed, to you fit in the tube send, it back to this laboratory, and, then a doctor that works for their laboratory, will. Review, the. Test. Request and. Order. The test and then, you get the results, online and you have the option, to talk to a genetic, counselor, when, you get those results. So, I think you know there's pros and cons of this like I said increasing. Accesses is really, important. In. Yeah. America. But, there are some concerns, in the fields about lack of pretest, counseling so, before. The test is done making. Sure people really understand, what they're being tested for and, then, when the results, are returned if people are really actually. Accessing. The genetic counseling and those, results are getting to their their. Actual, medical. Providers, and. Then. The. Main. Company, we, think that, of with direct-to-consumer, genetic. Testing. It's kind of the biggest player is called 23andme. You. May have seen, commercials. For this especially during the Olympics, they. Were really popular so. This. Is a company, that does. Health-related. Genetic. Tests and also. Ancestry. Genetic tests and I'm going to talk today, about the health-related. Some. Of the concerns with doing direct-to-consumer. Testing for, health conditions, and I wanted to start by using a, case, example, that came from our clinic it, was probably about five years ago but I think it illustrates some, of the challenges. So this was. Blue arrow points, to the patient, she was a 47. Year old woman who, came because of her family history of breast cancer. So. The. Circles. That are colored in shows that that person had breast cancer so in the, generation, above her that. Circle, that colored is her mom and she, is diagnosed, with breast cancer at 63, years old and then, this patient also had a sister so on the same row is her that other circle that's colored in is her sister and. She was diagnosed, at 35. With. Breast cancer, and. So that. Raises. Two red flags for us one, that there's multiple, people in. The family with breast cancer and, there's also that young age of diagnosis, for her sister, so. She came to the genetics clinic, and she had clinical, genetic. Testing for the brca1 and 2 genes and she. Was sent, have a mutation or what we call here at pathogenic variants, in, the brca2, gene, so, we know that her risk for breast cancer, is, significantly. Higher than the general population as. Well as her risk for having ovarian. Cancer, so. She was referred to talk, to the doctors at. The, Falcons Care Alliance about. Different. Prevention. And screening options. For her she chose to have her ovaries, removed and. Then she chose, increased. Breast cancer screening with MRI and mammogram. So. That all sounds great about one year later, she. Wrote to the genetic counselor I hope, you're doing well can't, believe it's been almost a year thank, you so much. I recently did the 23andme, genetic, test thanks, to my generous boss who gave it to me for my birthday, and she. Says the results came back that I have a lower than average chance of breast cancer, and that I did not test positive for, the BRCA, mutation, markers. 23andme. Mentions, their test isn't exhaustive so. That it doesn't look at all BRCA, changes. But, she says I feel like this information, disclosure could be easily overlooked. Or dismissed, by someone. In the general population so maybe someone who hasn't had genetic, counseling and clinical genetic testing and had that you know opportunity. To go through all that information says, honestly if, I'd done this test the, 23 me test and not spoken with you I may have received that the results of my 23 me and thought I was off the hook especially. Given that the other test is approximately, $5,000. So that was the clinical test she had was a quite. Expensive. But. Hopefully paid for by her insurance anyway. She says when you have a moment can you explain, why, my myriad tests came back positive, and 23andme, was negative, so. This. Was. Her. Actual test results, and you can see that, her breast cancer risk on the direct-to-consumer, 23andme. Report, was reported. To be lower, so, 0.8%.
I, Guess of the. Risk. Of a woman. In the general population and that she had an average ovarian. Cancer risk and then, here, it shows that. These. Are the, main, three the, only three changes specific. Changes that they look for in the brca1. And, 2 genes, and these are actually the changes, that are common in the Ashkenazi Jewish population. And. This patient did not have Ashkenazi, Jewish ancestry, so. So basically the. 23andme, test doesn't, look for all of the changes, and, would. Never find, the change that was in her and was definitely not the best test for her given her family, history in her ancestry. So. That raises, the big concern, with. Directed consumer genetic testing, for these medical conditions of misinterpreting. The results, so had she done the 23andme, at, first, as she alluded, to she would have been falsely reassured, and. Then conversely people can get results that could. Raise false, alarm for them as well. There's. Also concerns. About downstream, cost to the health care system we do have, a lot of patients who want to come to the genetics. Clinic to talk about their 23andme. Results because they they, don't provide, genetic. Counseling, to, help people understand, what the results mean as part of their service, and. Then also people may be wanting. Seeking, out unnecessary, medical. Tests, or exams based, on the results of those tests, I, don't, think it's clear the, motivation, of these companies, when, they're doing the. Direct-to-consumer genetic testing. That the. Goal is to to. Generate revenue, by selling the data the genetic information of, the people who, send it as a test and that is included. In the consent documents, that people sign but it really seems. Not to be transparent. That. That is the business model, there's. Also a different sensitivity, of the test based based on ethnicity so, you can see that just for the one example I showed where that test might actually be appropriate, for someone with, Ashkenazi, Jewish ancestry, who, is more likely to have those specific three changes but. Not really for anybody else there's. Also less regulation, so there's been news stories about samples. Being mixed up at, these types of companies and then if you were, to send your sample. To three different companies you probably get three different results, because they're looking at different changes, in the DNA, a and. Then coming. Up with different, risk estimates, based on those changes so how informative, really. Is that. So. Switching. Gears then to talking back, about clinical genetic, testing, and some of the new. Tests. That we're doing in the. Clinic and some, of the research. That we've, been working on in the last I, guess. Five years or so so. A little bit of background. I'm. Going to refer to exome. And genome testing. As, genomic. Sequencing. So. An exome, is the, part of the DNA that is the. Genes and it's actually a very small part of all of your DNA it's about one percent and. Then all of the DNA, is the genome so it's all the places in. Between the. Genes. Of your. DNA so, genome is basically everything exomes, just the part that makes the genes, and. That's not especially important, but the idea, is you know it's just a very, very extensive, test where. Those, panels, would be looking at you. Know like I said five genes 20, genes 200. Genes here, um, exome. Would be like two thousand twenty thousand genes. And. Again precipitated. By changes. In cost, so it became just a lot cheaper to get sequence information, from. All of the genes so so. We can do it with. The technology, but then the question is should, we and how should we do this so these are some of the questions that we have, been exploring. With. Bringing this genomic, sequencing, technology, into, the clinic, one. Thing is patient. Education so how should we explain. This test. To patients, and help, them make informed decisions, but. Whether they want the information, and also, help them understand what it means and then, with genetic, counseling, how is it the same or different than what, we've been doing for the single gene tests, or smaller panel tests, provider.
Education Specifically, for non genetics, providers, how to get them up-to-date. And give them the tools and resources they need and then. Which tests should we do, should we do a panel, should we do in exomes should we do a genome and one, should it be done for. Which patients, does it make the most sense to do these tests. To. Find an answer to what's going on for them and, then should it be done the, first time we see them or should we do some other tests first and then do an exome or a genome. And, a. Big question for us is how do we know which, variants, matter you find tons and tons of, variation, when you look at all, of the genes in someone's. Exome. So. How do we tease out which ones actually, may put make a person, more. Likely to develop a certain disease, and. What result should we return. We. In. The, next few slides I'll talk a little about patient, preferences, for what kind of findings they would want from these type of tests, but. Should we as a field, of geneticists draw any lines about which. Results. We should look, for. Like. Should we look for conditions, that would, affect someone's medical care even, if it's not the reason why they had the test done. So. How how broad should we when, we do that and then how do we deal, with different preferences, across. Different, people for what types of information they want how. Should we return the results. So. Some research. Has looked at whether returning. Information. Online is, a. Feasible. Thing to do maybe, over the phone with telemedicine, so, like a video match. With a phone conversation, or. In person as the way it it has been and then how to get this results in, the medical records so they're actually visible, to other health, care providers, and can be acted, on family. Communication, is a big piece because this, information, affects. Other family, members as well and then of course cost, and. How to get people access to this testing. And. How to develop. An evidence base to create rationale, for covering, for insurance. To cover these. New new. Genomic tests. So. The next few slides just highlight some of the. Research. That's been done funded. In the last, five. Ish years, and. This is kind of a blurry chart from, the. Four, studies that were funded, to explore. Genomic, sequencing, in newborns. So. Sick and healthy newborns, having genomic sequencing and exploring, how. Parents and doctors use that information, or. Like how helpful, that is with diagnosing. Undiagnosed. Genetic, diseases in those, specific populations. Sounds. Like some of the. Folks on this home might be familiar with all of us research program, at the NIH program. That's. Actually currently open for enrollment where they want to gather data on. One. Million or more people in the United States to help inform. And develop, they, call precision medicine so like personalized, medicine, treating you based on your genetic and. Other information. This. I just highlights a couple. Of the international. Programs there's, a lot. Going. On all around the world looking, at integrating, genetics, and genomics into. Clinical. Care. This. First, one is a program. Out of Melbourne in Australia where. They have several. Institutions. Where they're exploring. Genomic. Sequencing for 16 specific, diseases, and. Then trying to establish, protocols. And, systems to support integrating. Genomic sequencing, and then the second is a genomics, England where they want to do or they're planning to do a hundred thousand genomes. From National Health Service. Patients. Who have rare diseases their families, as well as patients, with. Common, cancers. So. As. I mentioned I was I've been working in. Genetics. And. Research. Here at the University of Washington since, about 2012, and most of my work was with this. NIH. Funded. Clinical, sequencing exploratory, research, consortium. Which. Lasted. The, first phase from, about. 2011 to 2017. And you. Can see on this map there's a bunch, of clinical, sites in. A coordinating, Center and it's yes a large selection sort of a project and the overall goal, was. Exploring. Integrating. Genetic, genomic, sequencing, exomes and genomes into, clinical practice it's. A pretty high level to.
Break It down. Some. Sites were doing genome some exomes some. Sites, where they were enrolling patients with cancer we're also doing tumor, exomes. And. There were a variety of conditions for, patients who are enrolled in these, studies and people who had, cardiomyopathy. Heart muscle problems. There. Was one that did, carrier. Screaming. Preqin. Couples. Who were thinking. About having children there, with one study for healthy adults, and. Then we had some pediatric, and adult cancer. So. One, of the. Important. Conversations, when things about exomes and genomes is, the. Difference between. Diagnostic. Results and what we call incidental, or secondary findings. So, diagnostic, results are their findings. That. Explain. What, is going on in a patient so for our breast cancer example person, has breast cancer you find a mutation of breast cancer genes that is a diagnostic, rule or. Like. A child who has some. Developmental, delays, you do a genetic test you find a change, in a gene that's been associated with intellectual, disability, that's the diagnostic, test the, incidental, secondary, findings are things that are not related to why you did the test so, for example in our breast cancer patient maybe you also find, a change. In a, gene, that affects their. Heart, muscle function, that's. Totally unrelated but, it's also medical. Information and so, this chart is from one of the early papers from, this user group where it shows, just a plethora of options that people, were given to choose from and the different types of secondary, findings, so. There's. Two. Kind of broad categories, of what we called medically, actionable so these are ones where you search something you can do about those results medically. That, would, ideally. Theoretically. Help. That person's, medical. Outcomes, so, there's some kind of screening test or treatment, option, like with a medication, that I think is beneficial. And then also non-medically. Actionable so. Information. Like carrier status there's something you could pass on to your child wouldn't, affect you or. Medication. Sensitivity, information. There's nothing you do about it now but it could be acted on later if you, were, ever prescribed, a relevant, medication, so you can see all the orange boxes are, places. Where participants. Had the. Option to choose. What type of information they, would want to know about, and. So overall if you look in the literature there's really a lot of variability and what people want and how they want it shared. With them and this needs to be looked at in the context, of someone's. Personal and family history, cultural. Differences, as well as the, population, so there are certain things to, think about with, pediatric, populations, like, parental perceptions, and the developing. Autonomy, as a child, we. Did some small, focus. Groups here at the University of Washington, before. We started our project looking. At attitudes. Excuse. Me toward, accent sequencing, and returning, these incidental, or secondary findings. And. We, found a range of preferences, for return of results so, some quotes here to illustrate some of the the different thoughts people had some. People wanted to know all of the information, one. Participant. Saying I'd want to know everything, I want no sugarcoating, at all others, were interested, in findings that are actionable, like I described, or, certain. So. The quote I think if I could be treated I would want to know but, if it's something that they may not be able to treat if it's something that they can't guarantee that I'm going to get or the percentage like 50/50 and I have to just live wondering about this others.
Were Wary of genomic, information. This. Quote I just think you could go nuts treating all these little possibilities. I mean it just seems. Like there would be no end to I don't know trying to research what you should be eating or not eating for this condition I would go crazy and. Whether. Or not people wanted information or. Certain types of results. Depended. On some. Of the features. Of the conditions, so one thing was treatability. Another. Severity. And, you can you can take a look at these quotes lifetime. Risk and. Family. Impact so what it means for people's. Children is, definitely. A big, motivator. So. At the end of the consortium. And we. Did. An interview project, with. 21. Of the different providers across, the different. Caesar projects. And. These providers were all involved in returning. Genomic. Sequencing, results to participants and. We wanted to ask, questions, about logistics, of how this is done participant. Patient, reactions. And. Also resources, and, in training that these providers. Who are returning results that might be helpful. So. Some context, a lot. About, half of the providers, that were interviewed, were genetic counselors, most. Of them had less than ten years experience with which is pretty actually representative, of the field of genetic, counselors it's growing. And young, and. Then. That. There were a very number of result disclosure, sessions. Across the providers. But most were done in person and most, included, both the diagnostic findings. Related, to why the test, was done and then secondary, additional. Findings. So. These are some quotes. From. Clinicians. Who were interviewed. Too. On. The reflections, how. On how the participants, reacted. So this first one is for participants. To how to diagnostic. Finding, the providers. Reflected. That those participants, seem to, show. That there was an end to the Odyssey, some relief. But. Also some, disappointment. And worry about the prognosis once, they have an actual answer maybe it's not the answer that they want, and. Then for more rare conditions, frustration. With, limited information and resources, so it's definitely. You. Know a mixed bag of of reactions, there and the quote here is the mother had. Become very happy with this sort of slow steady progress, her daughter was making, not knowing kind of meant there was no cap on how far and how her daughter to do all of a sudden getting a diagnosis, it surprised even her that her reaction was kind of a crap is there not these, are now going to be a limitation. So. Sometimes knowing is harder than not knowing for this particular. Family. For, positive, secondary, finding someone's not related, to the. Diagnosis. There seem to be curiosity. Confusion. Misinterpretation. And. Then sometimes information overload. So, the quote here the infidel, incidental, findings, have. Been unique in our population because I think they're already dealing with such a crisis, that for many of them I actually worry more about the fact that they're not going to follow up on the incidental, finding in the context, of everything else that's going on. And. Then finally for participants. Who got normal diagnostic. Results so. Normal test results the provider, sense disappointment. Unmet expectations. In. Confusion but also acceptance. Or relief. So. The quote here parents who go to internet who, talk about this read about this they, think that with this we can find a cure we, can find a magic change, I think that's abuse of this technology by companies, in many physicians as well. So. Some of the challenges, and lessons learned I think highlighted. In some, of those quotes, so. Multiple, results. Having. To return a. Diagnostic. Finding and a secondary finding, in. One, communication. With a patient, can, be hard time, consuming, so providers. Found that reiterating, information restating, the results was helpful, trying, to assess understanding. And maybe even returning. Results in multiple sessions might, be helpful and then they emphasize the value of following. Up after the visit. The. Question of unmet. Expectations came, up a lot in a lot of the research that we did with. This user consortium. Thinking. About how we present this test, does looking. At all of your genes and such, an all-encompassing way, to get. Sequence information. That. Maybe we need to kind of walk that back and really, focus on setting, realistic, expectations. When. We talk to patients about the test and then. Also uncertainty. Again, with the idea this is this awesome test, we can find all this information. But we don't always know what it means and we don't always know what to do about it so. It can, be helpful to reassure.
That Communicate. Communication, pathways are open and that we can. Be a resource for patients and families on an ongoing basis. And. Then to dispatch on training needs this is a huge, topic. In genetics. The. Providers. Who, were, interviewed. Expressed. Hesitation about, if non-genetic. Providers, have the training and resources to, incorporate. These new technologies. Into their practice, but. We need to acknowledge, a role for a non geneticists, because there's not, enough genetic providers. Out there and. Patients, just don't have access to, the quote here I think there's definitely a role for them I think, that I mean I think we're going to have to give up some ownership of some of our roles with our patients, because there just aren't enough of us to do all of this I think some of the more straightforward cases, there may be some of the more straightforward pieces, of cases and, things that you could quickly and easily educate, non genetics providers about and confirm their competency, about are things that they could. Be informed about so there was definitely some, you. Know positive hope for the future I do. Have one case example, that. Highlights you, know the need for. Continuing. Evaluation. And education. This was one patient in this from the tutor consortium, actually from our project here at the University of Washington who. Had a gene, change in a medication, sensitivity. Drug. Yeah. Medication, sensitivities, genes that. Affects. How people. Break down warfarin. So it's a blood thinner and, basically. This this gene change means that this person could, probably have a lower dose of warfarin when they start. And. This information was explained, to the participant. In, person, and they were given a report but. We received an email by month later. Saying. The next study that, was our clinical, study here at u-dub indicated, I have a moderate sensitivity, to warfarin, with that information I switched to Xarelto, one of the new blood thinner drugs to, mitigate that sensitivity. The next study provided this useful information that I acted on I feel very fortunate to have been able, to be. A part of the neck study and benefit from its result this, participant, felt, very positive about his experience. But. This was an inappropriate. Change. In in care based on this result. There. Was there's no reason to change medication, because of a sensitivity, to when, this the warfarin was initially, started. So. We're, not sure you know all the nuances of this this, switch but it, just highlights the need for you, know us to do a better job in the whole community to. Try and, help. Patients to make informed decisions and, understand. This genetic, information what, it means for them. So. Key findings from that project, for, returning results or. That it's similar returning, results from genomic, sequencing, tests to traditional, genetic, testing, but. That there are some nuances, because. Of the additional. Complexity, of the tests and the possible, results and then the potential uncertainty. Like. I said managing, expectations. Continues. To be an ongoing challenge. And. That we need to do. Future research on, the patient experience, and their understanding and follow-up, of recommendations. So. Moving forward. The. Current. Project. That I'm working on is part of phase 2 of the Caesar consortium, and you, can see the title has changed to evidence. Generating. From. Exploratory. So the, focus is definitely on. Developed. Furthering. The evidence, base for how, to best implement genetic. Sequencing, technologies, and then, also, importantly. For this consortium, there, is a focus, on a. Broad. Spectrum of health care settings so more community. Hospitals, community, outpatient.
Clinics And also. Enrolling ancestrally. And socioeconomically. Diverse patients. Each. Project has to enroll at least 60% of, participants. Who, meet, that. Criteria, so. Really. Looking forward to making, our, information, more generalizable, and meaningful, for for people across the United States so. Very. High level summary clinical, genetics and genomics is constantly, evolving. And we internet account let's play a key role and there's. A much to be learned still to responsibly, implement, genomic medicine in, clinical, care. So. I have some. Poll questions I, think I need to, switch. Back, to Maddy yeah. Okay. So I'll stop sharing now. Okay. So. Oops let me. Set. This up. Okay. So. The first is kind of a Content, question. And. It. Kind, of puts you in the position of a genetic counselor and then of course there's a lot of factors to consider but. In this context. So you're Janet counselor and you have a patient who's a woman who's diagnosed with breast cancer at 40 years old what. Would you recommend for her, would you recommend a, color genetics, test. 23andme. Testing. That. She just go to jannat counseling to talk about genetic testing. Just. Brca1, and 2 testing, or a big gene panel that includes brca1, and 2. About. 3/4 of people have responded so far. Wait. A little. Bit longer. Okay. I'm gonna close, the poll and anyone. Who's in the middle of responding, will have a 20-second, countdown I think to. Submit. Your final response. Ten. More seconds. Here, you go okay. Great. So, it sounds like yeah the majority of folks would send. Someone to genetic counseling to talk about genetic, testing, you. Know I think if you were taking genetic counseling boards that would be their right answer, I, think, the only answer that would be definitely. Not the right one. For me, and for most clinical genetics people would be be, thinking, of just doing a 23andme, test. Yeah. But but yeah the idea of brca1. Or 2 versus, a gene panel, is just is a question that it kind of provider-specific, where, I think most providers are looking at panels now but it's, been like a gradual, shift from, looking. At just a few genes to to, a lot that's. Great ok and let's go the next one I guess ok, so this is a more, of a personal question. What. Type of information do, you think you would want to know if you are having a genomic sequencing, test, so. Information. About a condition, with medical, treatments, or prevention conditions. Without medical, treatments, or prevention what, maybe there are lifestyle changes, you would make or insurance changes. Conditions. That could affect children, or family members or and. Or medication, reaction, or dosing information. Ah. And, there's no right answer obviously to, this one. Yes. Lore I got to thinking that we maybe should we, should have included one that said I, have. No idea, oh yeah. Looks. Like most people have response sometimes I don't even know and I think about it all the time.
I'll. Show you those results in just a few more seconds. Yes. I just think it was kind of an overwhelming question. Yeah. Yeah. Yeah. I'm not sure how I asked what, answer I got. Bored yes I, can't, I can't answer the poll question so. You. Guys are supporting what's in the literature about you, know people, typically. Do want the information but. There is variation across, people. Yeah. And that can change over time and, context. Great. I'm, sorry there's I think there's one minute left over, questions are can we I don't know yes there, are several in the chat, box that came, in while you're talking so, I'm going to go through it and if you want to go through it you can to quickly. Say I'm going to post the link to the, evaluation and. MLA C yes, I fancy, box Thank, You May for, those that you that, need to leave early, feel. Free to do that, one. Of the questions was. I. Did, in ancestry.com. DNA. And downloaded, the raw. Results, where can I find out how to interpret, those results. Yeah. That's tough it's apatite that leads, to or addresses, a question of, like downstream. Yeah. Management. Of the information. So. There are. Companies. Where, you they'll, like interpret. Your. Raw genetic. Information, but. Most of the ones I'm familiar with are about, health information. So. I wonder, the best way would be to contact the ancestry, company, because. I haven't really heard about them giving you know raw data. The ancestry, portion of direct-to-consumer. Test. Although that sounds like that's what happened. So. Hopefully, they would you know have some resources, to direct. You. Yeah. And I think yeah, I think she's referring to the DNA, of the ancestry.com. Beat, well, maybe maybe, not I was thinking maybe she was referring to the help aspect, yes I think do they do health, or not, some. Of them do yes, like 23andme, does health yeah um but. It's you know it's hard to those are companies where. It, depends, like which one you send it to they might send you a different result as well but but you can definitely, yeah. Like. One of them is called Prometheus, to interpret. Genetic. Health variants. Like, raw data yeah. We. Have another one here and how accurate, is testing, done with saliva as opposed, to no, mispronounced this this whole scraping. Yeah. Yeah. Oh goodness. You'd have to you need to check with, the laboratory, that's doing, it because they need to do, like. Validation tests. And. I think it can depend on what is being tested for because. When you do buccal straight things you can get at like contamination. With bacteria. I'm not a molecular, geneticist but, this is why. Yeah. What. I think, isn't is. Part of the consideration, with that so. Yeah. I think it's important to think about the check with the lab that's doing the tests to make sure they're validated, to do it on that type of sample, and then the.
Type Of test that it's for, and whether that makes a difference. Another. One is do you know websites to speak more to the two methods you mentioned, do a sequence, alignment, and compared, to a reference genome to. Get the variance for non, Genesis. Audiences. Website. Yeah, so most, of the tools that we have that, compare. Genetic. Variants to. Reference, sequence are pretty, complicated, there's. I'm like, the. One site called the UCSF, genome, browser. But it's pretty it's, not like, general. Population, friendly it's not even like per patient, per arm like position, friendly, it's like geneticist. Friendly. So. That's probably not, a great one there is a catalog. Of, genetic. Variants that have been found by laboratories. Called. Clinvar that, is, a little, more accessible, but. Still also aimed. For. Providers. I wonder if this person maybe could could email me directly so, i, could get a better sense of the question. Yes. We could have them yeah go. Ahead and yeah, your emails right there on the screen, yeah we have open warrants I think we can fit in here, okay. I'm not sure if you would, know this if the million, veteran, program is, partnered with the all of us research. Oh yeah. I'm not familiar yeah. I was, assured that either that might be something that we. Could, contact. Them for, emissions. We can find the. Other is let's, see. Let. Me check here. See. I'm looking through this. There. Was when I submitted, 223, years, ago I recently. Asked, for my sample to be destroyed, and revoked my consent, to use my data and the, other advice on how to protect my info. Mm-hmm. I think. Those are great steps. To. Take. It's. Hard, to know you know what would have been done prior. To revoking. That consent, I. Don't. Think yeah that I have any other specific. Thoughts. Beyond. Contacting, the company, and seeing yeah I mean those sound really like very. Good questions, good, things yeah um. Let's. See anything else I. Don't. Think there's another one that we've missed, if. I, have right and. I apologize. As I've done that so, free to email myself, or, Laura and we. Will try to get that answer to you, but. Due to the, time, constraints, that we have here I just want to make sure that people can take the. Webinar. Evaluation survey. That we have that. Will be done to getting. That MLA, Cee and again. Even if you don't want the C, e we would really value your, input, regarding. The, session, I, also. Wanted to tell you a little bit about, the. Next session of the PNR rendezvous, which will be September 19th, where. We will be. Speaking. With the executive, director and Public. Engagement Manager of Northwest, Association, for biomedical research who. Will be presenting about, their work focusing, on a project, of theirs called community, conversations. That. Were held in the region's, to build trust and support, of stem we. Hope you will consider attending, that session and. Mady's. Could be linked for, the information, as well as if, you want to register is not required but we do encourage you to do so you, can also see the recordings, of past sessions, as well and. We. Want to give to Laura a big thank you for, coming and presenting to, us this, is a fascinating, topic and. A, lot to take in and we, thank all of you for coming and attending so. Have a great rest of the afternoon and we hope you will. Join us for the next session in September thank. You thank. You so much.