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Sara: Welcome to the Positive Gene Podcast. This is Sara Kavanaugh, your host. This show is dedicated to empowering individuals managing hereditary cancer risk. We share stories, we get expert insights, we have practical tools to navigate our unique journeys. Today I'm especially excited to bring you an in-person episode from the Vanderbilt Ingrid Cancer Center in my town of Nashville, Tennessee. I am here at the ICARE Registry initiative, a groundbreaking program that's advancing the understanding of care of hereditary cancers. It is such a privilege to be here at the center, meet the staff, and just to see their work firsthand. So joining me is Dr. Tuya Pal, a board-certified clinical geneticist and the principal investigator of ICARE initiative. Dr. Pal is a professor in the Department of Medicine at Vanderbilt University Medical Center and the associate director of cancer health disparities at the Vanderbilt Ingram Cancer Center. Her leadership in hereditary cancer research and dedication to patient care is inspiring to say the least.
So let's get started on this fascinating conversation. We're going to learn about ICARE, we're going to learn about Dr. Pal and the impact that this organization and others are having on the hereditary cancer community. So welcome to the show.
Dr. Pal: Thank you for having me.
Sara: All right, we're going to get started in opening up with asking you to share a bit about your journey. What inspired you to specialize in hereditary cancer genetics? And then it ultimately led you to an initiative like ICARE.
Dr. Pal: Yeah, so thank you Sarah for the opportunity to be on this podcast. When I think about from an early age, I love genetics. And then during my pediatric residency, I really thought seriously about doing oncology. So it kind of came together with doing genetics and oncology all at the same time because as I was doing my fellowship, it was in the early 90s when the BRCA genes were just in the process of being discovered where this field was starting to materialize and really become meaningful in terms of patient care and trying to influence, you know, improving outcomes based on genetic testing for inherited cancer. So that's how that all started.
I started my faculty position at the Moffitt Cancer Center back in early 2000. And what I noticed at that point was, again, there was a lot of direct to consumer testing in Florida at the time. There was the patent on the gene. So, you know, only one company could do the testing. There were a lot of issues with access to testing. So a lot of those shaped my early thought process in terms of, well, how can we democratize genetic testing and positively like influence outcomes? Because that's, I think, what this is all about, using genetic testing for as many people as possible to empower them to positively influence their health.
Now in Florida, again, at the time there was really a shortage of genetics professionals. A lot of people were doing the genetic testing. Sometimes it was direct to consumer. So again, that brought up everyone wasn't getting the same advice about, well, what are the next steps? What should you be doing with your care? So we started building a network of providers.
And this was, again, with grant funding. We were lucky enough to secure some grant funding where we were able to partner with providers, provide them with educational opportunities, engagement opportunities, focused on inherited cancer predisposition. We'd been hosting these monthly case conferences where we bring in guest experts. So again, this started happening around 2010, so about almost 15 years ago. And through this effort, again, the vision was that through these partnerships, these individuals, these providers, are seeing the patients with hereditary cancer predisposition, people who either have a mutation, have cancer, are at risk for cancer, et cetera. And they themselves don't necessarily have a place to send them if patients are interested in research opportunities or clinical updates, et cetera. So we built ICARE so that anyone can refer their patients to ICARE.
Once they are in ICARE, again, it grows our registry, but it also enables us to do our own research studies and collaborate with others and support translational research studies. So that's kind of what the vision was. Quite honestly, when we started, I would not have imagined how much we've grown because in the early days, again, we were having referrals, but not at the magnitude that we're having. I think we're going to surpass a thousand consented participants this year. And these are, the minority are actually Vanderbilt patients. Most of them are from outside of Vanderbilt that are participating. And I think what has been at the core of ICARE from the beginning is we don't want to collect people's data and not do anything with it and not go back to them. So engagement has been at the core of everything we've done.
So as examples, we do newsletters every six months where we include information that we think would be of use or of interest to individuals with inherited cancer. So if there are guideline updates, we will put that in our newsletter. New studies that have become available that are published or research opportunities, clinical opportunities.
Again, I'm not going to say that it is completely comprehensive, but we put in tidbits that we think will be of interest to the inherited cancer community. Beyond that, what we do is we know that guidelines change at least once a year.
So as guidelines change, and I myself am a clinician, so I'm a practicing physician at Vanderbilt, and I see patients in the hereditary cancer clinic. And I do do the management plans for these individuals. I see some people on an annual basis for ongoing management. And what I find is even within the context of our clinical practice, we don't see everyone annually. And in between, how are they getting updates about, okay, well, maybe you don't need to do something or maybe something else was added.
So through ICARE, what we try to do is if there are guideline changes, we know the hereditary mutation is for our participants. So we will email them that, “hey, this changed in your guidelines”. For example, with BRCA2, just a few months ago, we changed the NCCN guidelines to make it to state that anyone with a BRCA2 mutation, regardless of family history, could consider pancreatic cancer screening before it was based on family history. So once that change happened, we actually emailed all of our BRCA2 carriers in our registry to give them a heads up.
Again, we are not their clinical providers, at least for the majority that are outside of Vanderbilt. So I'm not, I don't consider myself their physician, but it's another way for them to get information in their hands to then go to their own providers to be able to get information. So I do think that engagement has been at the core of our efforts from the beginning. And I think that has been key to our success because we aren't trying to hoard data.
We are trying to be collaborative, both nationally, internationally, locally, and we are going back to our participants. Anytime we use participant data and it gets published, we will highlight that in the registry. So people know, like some people participate in our registry because they want to contribute to the larger research mission. They want to move science forward. So giving them that information that, hey, we use this and here's how it moved the science, I think is meaningful and impactful to them.
I mean, again, I'm kind of assuming these things, but that's kind of my vision for why we have experienced the success we have because it is beyond what I ever thought could be achieved.
Sara: I mean, just as somebody who is on the receiving end of that information, it's huge. You had mentioned the BRCA change, BRCA2 change. And for me specifically, as we had spoken to earlier with my check to mutation, having some slight changes to maybe what my screening protocols are because my variant had, they've sort of scaled it back. So having that knowledge is really priceless. I mean, I can take that now to my breast specialist and say, what is your recommendation?
Dr. Pal: So you are the exact participant that we want to be educating and everyone doesn't want the information. So it's up to you how much you want or don't want, but I think we should make this education available. On top of that, through ICARE, what I find is we have this opportunity to target information, right? Because what we have also learned through our research is when you're very general, it's less meaningful to people, right?
So if you're not gene specific and you're kind of talking in larger terms, yeah, you're educating, but people want to know, well, how does this affect me, right? Like if you have Lynch syndrome due to MSH2 versus Lynch syndrome due to MSH6, like people want to know, well, okay, I have MSH6 associated Lynch syndrome. What should I do? What are the national guidelines? So that's what, again, through time, because sometimes there are advantages of being general just from a scalability standpoint, right? Like things aren't changing as often.
You can kind of be general about, okay, well, once you have a gene mutation, it can affect your cancer risk, which then can affect your cancer risk management. So that's kind of the principle of how that continuum works. But then as a carrier of a BRCA2 mutation, I really haven't told you, well, what are your risks? What should you do about it? So that's what we've tried to work towards, and that's certainly the feedback that we've gotten. So again, all of what we try to do, we try to make scalable because we want to be able, like I said before, democratize genetic testing and have an impact on making information accessible for all as more and more genetic testing gets done. But again, you need an infrastructure to be able to do that, and those are the directions that we've tried to head.
Sara: You mentioned one accessibility in my mind that provides a couple of different ways to look at the context from that. And so one example of accessibility might be, it's easy to understand in terms of being accessible. You guys are your newsletter, for instance. You're not from what I have found, and even participating in one of your case conferences that was really geared towards, you know, patients and patient experiences. But accessibility in terms of making the information easily digestible, easily to act upon.
So talk me through how you guys really are mindful of, as you're approaching patients with the information, making it easy to follow, understand, and again, to be able to react to what their predisposition is and what to do, does that make sense?
Dr. Pal: That completely makes sense. So that's a great question. The case conference that you attended, I would say in general is provide, it's open to like when we make it publicly accessible, that truly means publicly accessible. So anyone can participate. But through ICARE, we also need to be mindful about like, who is our target audience, right? So with the case conference, our target audience is the providers. So we need to be mindful of speaking to them at a level that they are going to be able to enhance their professional development. So that's where I would say those are not patient focused.
However, I think patients could potentially benefit from attending or going to our YouTube channel, like say, you have a PALB2 mutation, you want to learn more about it from a leading expert in that field. We have talks focused on that on our YouTube channel. However, they're not patient focused. So because that wasn't the intended audience. We have started another effort in the last few months where we had patient forums for ICARE participants. Again, they were met with mixed, I mean, they were met with enthusiasm. But again, sometimes we had more of an audience, other times we didn't. So again, those are talks that are also available on our YouTube channel. And I would say those ones are more patient focused, right? So I think audience is really important.
Now, speaking to accessibility with understanding the information, again, with genetic information, sometimes some of the words we use or the jargon, it's very hard, like when you typically think about what is the grade level, it's very hard to get genetics down to a fourth grade level, for example, just because of the words that we don't have a substitute for. But in our efforts, we have tried to, so the newsletter you asked about, I try and be as clear as possible, but the audience is both providers and patients. So I'm trying to kind of get a balance there. Could we be more accessible to our patient population? Probably we could, but I see that as a call to action because again, those little snippets that we're providing in the newsletters are not enough for someone to completely have a good understanding, right? But if we've been able to tell you, "Hey, there is something different about CHEK2 that you might want to go ask your doctor about," in my mind, that's a success. Because even if we haven't told you exactly what the details of the study were, we got you to think about acting. So that's how I see the newsletters.
You know, the other things that we've done, we've tried to... Like one of the barriers to getting services sometimes is getting the education, getting genetic counseling. Again, seeing a genetic counselor, I would still say is the gold standard before you get the text, right? So that they can walk you through the pros and cons, do a risk assessment, etc. Sometimes you don't have a genetic counselor in your area. Sometimes, you know, maybe you're lower risk and there are ways of automating services.
So we have a study, it's called our TIPS study, where we've tried to automate at least the education piece of it and collect survey information to be able to provide personalized assessments about, "Okay, do you meet NCCN guidelines for testing? If you've already had testing, what does your test result mean?" Like interpretation of test results, and then what are the NCCN guidelines in terms of management recommendations? So with TIPS study, we're trying to, again, democratize the information about care in individuals. But as part of the assessment, I'll say that this has been a learning experience for us because with the automated education we provide, we've really tried to intentionally bring down the grade level to make it more understandable across the board. Again, is it perfect? No, it's not. But there have been specific efforts to reduce the grade level and to test it to see, "Okay, how much do you know before? How much do you know now?" in terms of knowledge, informed decision-making, and then our assessments, which I consider a key part, also having that reviewed by various experts and seeing, "Well, how can we make them as useful as possible to our participants and eventually patients so that they have the information that they need in order to act?"
So I think that is part of our efforts, but I mean, there's a lot to do in that area. I don't think everyone always, like even when you talk to them, it can't be a one and done sort of thing, right? Because what you hear, like people come to us at different points in their journey. Some are trying to do the testing or considering the testing before they get a cancer diagnosis. Some are in the midst of a cancer diagnosis. Some are like following a cancer diagnosis.
So we get a heterogeneous or a diverse group of people and everyone's got different needs. If someone's in the midst of a cancer diagnosis, they're not going to want a one-hour appointment about talking about their future risks. They're trying to deal with their current risks, right? So I think we need to be giving people what they need at the right time where they can digest it. So that's why, like with our TIPS study, that's kind of how we designed it, where you can get the information at any point prior to testing, after testing to interpret results. So it's a resource that we provide to anyone that wants to participate.
Sara: That’s great. So first the process is somebody's connecting with you to connect with ICARE. It's going to come from a different source potentially. It's either going to be their geneticist, maybe, or like me, it's going to come from, I just connected with you through FORCE who is Facing Our Risk of Cancer Empowered and many of you folks…
Dr. Pal: Just a nice story about FORCE. So Sue Friedman is a personal friend. Oh, she's the founder and executive director of FORCE. But when I was at the Moffitt Cancer Center, that's where we started ICARE. Sue was part of ICARE at the beginning. So she was right at the ground level working with us. So I've known Sue for years. She's wonderful. And FORCE is an amazing, amazing organization.
Sara: It is. And I tell you, they help us get so connected and feeling more in control and more empowered over our experience because we do have access to all of these resources. So let's talk, let's go back to the TIPS resource. So if somebody's interested in this, what is the process? How did they find it? What did they do to get connected with that particular initiative or that study?
Dr. Pal: So it's basically just enrolling online. There's a link that we have. You can just go to our Inherited Cancer Registry or ICARE website and under the our research tab, TIPS study will be there. And so you can learn more about it before you decide if you want to participate or not. And then there's a direct link on that website to take you to the consent form and then complete the surveys. Once you complete the surveys and you have the option to watch the video just to get, it's an interactive video to learn more about inherited cancer, predisposition.
It's kind of like choose your own adventure where you can learn more about certain topics if you choose to. Once you complete the material, whatever material you choose to complete, we will send you an assessment within a few days. And with these assessments, like if you complete the family tree, we have the capability of automatically generating a three-generation pedigree that then gets sent back to you as well.
So some of these things I do think are helpful even if you need to speak to somebody else, which, you know, I would advise that if you have an opportunity to speak to your doctor or speak to a genetic counselor, participating in TIPS is still potentially going to help because you'll already be going to them with some information and an assessment. And, you know, quite honestly, some of these family trees can take 30 minutes to draw. You've now saved your own time and the time of your provider by having that already done.
So, again, and we will go through based on the information you give us an assessment that's tailored to you. It's not going to be personalized, this is what you should do because that would be your medical provider. But we can take a step back and say, okay, you have checked to you, you have this specific mutation, here are the national recommendations.
Sara: Okay. So what types of individuals or families may be best suited to participate in ICARE?
Dr. Pal: So anyone who -- so our eligibility criteria is very broad. Anyone interested in participating in studies focused on inherited cancer. So it could be, again, I would say that the majority of our participants are individuals who have an inherited gene mutation in a cancer gene, like in a hereditary cancer predisposing gene. And, you know, my personal opinion is they are the ones that have the most opportunity to potentially benefit, right? Because the information we are disseminating through the registry through engagement activities are focused on inherited cancers.
So I wouldn't say that someone from the general population is going to necessarily benefit from ICARE unless they have some interest in learning more about inherited cancer predisposition, either at the provider level or at the patient level.
Sara: Yeah, that was going to be a question as well, is the impact on healthcare providers. We've talked about the case conferences they have, but if we do have healthcare providers that are listening to the podcast, what other benefits do you see for them in becoming more involved?
Dr. Pal: So, again, we've had -- I think we've had over 500 healthcare providers at this point over the last almost 15 years engage in some way with ICARE. We have, you know, hundreds that have referred to the registry. I'd say the benefits are, again, I would say it for myself as well because I'm a healthcare provider. I don't have the resources to follow up with all of my patients with inherited cancer predisposition on an annual basis, right? However, guidelines are changing on an annual basis for that gene every year, not necessarily, but we don't know which gene it's going to change, like guidelines are going to change for.
And so through ICARE, it's a way of having their patients kind of connected. Providers also often see the benefits of, you know, supporting the broader research mission, right? So, it's a way of linking their patients who are interested in supporting the broader research mission beyond that, even participating in certain studies that, again, it's research, so we can never guarantee benefit.
But as another example, we have a hereditary breast cancer study focused on BRCA1, BRCA2, CHEK2, ATM, and PALB2 through which we are able to do tumor sequencing. And this is -- tumor sequencing for breast tumors. This is a study that I'm working closely with my colleague and friend, Dr. Sonia Reed, who's a breast medical oncologist. And that kind of study, again, people aren't going to necessarily get breast tumor sequencing if you have an early stage breast cancer because that is not standard of care. So, there are certain things that may be offered that you wouldn't necessarily get. So, we have our own focused studies.
Another study that we've been working on for the last few years is our Impact Study, which -- the segue of which is through ICARE, where we're testing strategies to improve both cancer risk management for individuals with hereditary cancer predisposition, as well as family communication.
So, again, if a patient is interested in these kinds of efforts, I think there are benefits at the patient level. And at the provider level, as they refer patients, they do get -- they become eligible to participate in our case conferences live. Again, some of them are open to the public, others aren't. But even the ones that aren't open to the public, providers would have access to. So, I think there are various potential benefits.
Sara: Yeah, that's great. So, you're leading these fantastic research studies through ICARE. Are they in partnership specifically, say, with Vanderbilt or other, you know, academic or research organizations, or is this something that you guys sort of lead the effort and you pull in resources?
Dr. Pal: So, it's a combination, I would say. So, we have collaborators where we are sharing de-identified data, both nationally and internationally. And by de-identified, I mean, yes, we collect data through ICARE, but there are regulations where we're not going to be sharing any identifiable participant information. But in order to move the science forward and pull resources, you know, internationally and nationally, we have to get the data all together in order to figure out, okay, well, how are -- what is the natural history of a certain condition, et cetera.
So, I would say some of the efforts we lead, others we collaborate, we're kind of a support where we're submitting data to others. So, it would be a combination. I do feel strongly that when people participate in ICARE, they are participating to move the research forward. So, we are not -- we cannot be hoarding their data for our own purposes. So, it's something where we are collaborative.
Again, we don't have infinite resources, but we try to share some of the things that are easy to share. We are 100% on board. Some of the things that people ask us for are going to require additional funding. So, we're not in a position to support someone else's research study, but again, if there are, like, we have students who ask for us to send out certain things through ICARE or publicize something, which, you know, again, depending on what it is, we are happy to consider doing. So, yeah, I would not say that everything that we do is our own effort. Some of them were support. Some of them are our own.
Sara: Yeah. Okay. And I love that the fact that you just mentioned, you know, all of this effort is to help move the research forward. The more data that you have to work with, the more patient experiences you have to work with, the sooner we can get more clarity on our pre-dispositions, how we manage it going forward. I mean, to me as a Previvor, that gives me so much more peace of mind when I can say clearly that there are people who are working super hard to make sure that we find a solution to this, you know, whether it be, again, managing it in a different way or in an underway, the communication piece.
And we weren't just talking about the physical, medical side of things. We're also talking, like you said, on the Impact Study, like how people are coping with us, how do we communicate with these things. And I think that that goes a long way because this is really cancer and cancer predispositions are often, you know, we talk about it often, or we should talk about it more often about the holistic person, right? This is just dealing with a physical diagnosis. There's so much more that comes with it. So I appreciate all of that.
Let's talk about one more issue before we wrap up, and that is addressing health disparities. So there are health disparities in genetic testing, in counseling that remain a challenge. Do you see any progress being made in this effort for underserved populations or what work still needs to be done in this space?
Dr. Pal: I think there's a lot of work that still needs to be done. Individuals from underserved communities, whether that's based on race, whether that's based on socioeconomic, are not getting tested at the same rate. You know, I missed rural reality. Again, we live in a pretty rural state. So, again, I think there are many factors that lead to under testing. Under testing then means that people are not getting the opportunity to know what they're at risk for or getting cancer diagnosed at a later stage, which then has downstream impact. So are there strategies? Yeah, there are strategies. Has anything really meaningfully worked yet? Not necessarily. I think as we, I think the main message here is genomics has tremendous opportunities to improve health, right, to guide healthcare. At the same time, genomics has tremendous risks of widening existing disparities, right? So the disparities we have right now could become worse because the people that have are going to have more. The people that don't have are going to have less, right? Because, again, we've been kind of talking about germline testing, meaning testing of your the DNA that you were born with that predisposes to inherited cancer.
But then there's the tumor DNA that also we are often testing separate from the germline DNA. So when someone develops a tumor and that can guide treatments. But again, is the entire population getting access to tumor testing? The national data says no. So I think that there are efforts to try and level the playing field so that all populations can benefit from genomic advances, but we have a lot to do.
Sara: I think I will invite you back to talk in greater detail about this because I think there's a lot of work to be done as well. And I know you guys have the Be Great initiative that focuses on the Black community and understanding hereditary cancer risk. So I would love to see several months down the road we can reconnect and learn more about the efforts that you guys are taking there.
In terms of wrapping it up, then let's talk about what's on the horizon for ICARE. So upcoming, other upcoming initiatives or things that you want us to know about?
Dr. Pal: So with ICARE, I mean, again, I think that actually what is exciting is next year will be our 15 year anniversary. So we are excited about continuing our case conferences, our case conferences are continuing to grow. Our base of participants continues to grow. I don't know that we're going to change course, but there will be additional studies that are ongoing. I am excited about our PALB2 effort that's been going on for years at this point. That's a collaboration with my Canadian colleagues, Dr. Kelly Metcalf and Stephen Nairod, where we are actually trying to understand the natural history of PALB2.
And just so everyone is familiar, we have BRCA1 and BRCA2, which get a lot of press. But if I were to think about the third most important gene for hereditary breast cancer, it would be PALB2. And I think many of us in the field feel that way. But yeah, we don't have the same depth of data in PALB2 as we do for BRCA1 and BRCA2, right? So to kind of bridge or fill in some of the information gaps, we've been doing work to understand the natural history of PALB2 through an observational study. And again, through ICARE, we've actually been able to grow into one of the largest PALB2 registries, the highest numbers of PALB2 carriers in a single registry over the course of the last several years. And really the focus of this effort would be to see, well, what kinds of breast cancers do PALB2 carriers get? And what are their treatment outcomes? What are the types of treatments that tend to work versus not work? And what are their outcomes in terms of breast cancer recurrence, survival, et cetera? And I think those are the kinds of studies that we and others are working on at this point. We have similar efforts for ATM and CHEK2 carriers as well. So I think those are the things that are on the horizon.
There are many other things on the horizon, but that is one that I'm really excited about that I'm hoping we'll have some data for it.
Sara: Well, we will watch out for it.
Okay. Where can our audience learn more about ICARE?
Dr. Pal: So we have a website that I am hopeful is user friendly. It's inheritedcancer.net. And on there, if you're interested in learning more about different topics, we've tried to make our search engines as friendly as possible. So you can just type in keywords and you can learn about, have we done a talk on it? Have we published an ICARE newsletter with an article focused on the topic you're looking for? So the search functions should be active.
If you want to participate in ICARE, there's just an enroll now button or join us button through which you can consent directly online. So again, if you have questions, there's an email address that you can reach out to directly, ICARE@inheritacancer.net, but there's also ICARE@vumc.org.
Sara: Well, Dr. Pal, thank you so much for taking the time to join me today. I really appreciate it. And it's so incredibly helpful to see the incredible work that you guys are doing here at ICARE. The dedication to advancing the research and the studies is really amazing. And I'm so thankful that we crossed paths.
So to our listeners, if you'd like to learn more about ICARE and amazing resources they provide, again, visit their website, inheritedcancer.net. You'll find information on joining the registry, ongoing research and educational resources. I will have all of the links in the show notes on the podcast blog as well.
As always, stay connected to the Positive Gene podcast on social media @positivegenepodcast or the website www.PositiveGenePodcast.com.
I also have a survey out there right now on Instagram asking for ideas on the show. I'd love to get your feedback and be sure to join us for our next episode. I'll be talking to Dr. Brian Shirts from Connect My Variant. This is an innovative nonprofit building communities dedicated to helping families communicate genetic testing and hereditary disease prevention. So it's an episode you don't want to miss.
And then finally, I'm going to remind you, you're not alone on this journey. There is this whole community of support and together we can navigate these challenges and find strength in our shared experience. So thanks for listening and I'll see you next time.
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