Dr. Bryan Schneider and Dr. Milan Radovich return to the podcast to break down the latest developments in personalized genomic medicine, share findings from their triple negative breast cancer research, and talk about their current and upcoming breast cancer studies, including EAZ171 and PERSEVERE.
Aaron: Welcome back to the Healthcare Triage podcast. We have two returning guests today: Brian Schneider and Milan Radovich. You may remember them from the previous time we talked about triple-negative breast cancer. So we're going to talk to them again and get an update on some of the research that they've been doing, plus the discussion again about breast cancer, how it's treated and what's going on at IU and beyond. Brian is the Vera Bradley Professor of Oncology and Director of the IU Health Precision Genomics program. Milan is an Associate Professor of Surgery at the IU Simon Comprehensive Cancer Center and Co-director of the IU Health Precision Genomics program. So both of you, welcome.
Brian: Thanks for having us on.
Milan: Thank you for having us.
Aaron: This Healthcare Triage podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research and patient care. IU School of medicine is leading Indiana University's first grand challenge, the Precision Health Initiative with bold goals to cure multiple myeloma, triple-negative breast cancer and childhood sarcoma, and prevent type two diabetes and Alzheimer's disease.
Aaron: I want to start, if we could, with a reminder for people who might not have been listened to last episode about what exactly triple-negative breast cancer is.
Brian: Triple-negative breast cancer accounts for probably about 15% of all breast cancers in the United States. Although it is less common, it is one that we think about a lot because the treatments are less good and the mortality is much higher. Triple-negative simply means it doesn't have one of the three receptors that are really important in breast cancer, which include the estrogen receptor, the progesterone receptor and HER2.
Aaron: So when you talk about receptors on breast cancer, and you mentioned three, what does that mean? What are receptors with respect to breast cancer?
Brian: Receptors can be an over expression of a protein or simply, an area that the cell uses for signaling. So you think about it as the way a cell survive. It uses these receptors, if you will, to help stimulate them to live and divide and turn over. The way I describe it to patients, it can be like an accelerator on a gas pedal on a car where if you have too much of a protein and then you're receiving the signal, the cell can begin to divide too much or in an uncontrolled way, and this essentially is cancer. What we know is that breast cancers, in particular, often have an over expression of an estrogen receptor, which means it's fueled by the hormone estrogen.
Aaron: You're saying the breast tissue in general usually has these receptors, but for some reason, either there's too many receptors or the receptor just when it gets estrogen, just reacts too much, or is it both?
Brian: As we think about the strength of a receptor's expression, I think of it often like a dimmer switch on a light, and sometimes that switch is turned up too bright. In the case of breast issue, indeed much breast tissue has normal of estrogen. But again, the cancer cell has capitalized on this growth signal in a way that it uses estrogen as a fuel to survive and become essentially immortal.
Aaron: Milan, when, when breast cancer cells have these receptors, do we use those to treat the breast cancer?
Milan: We do. So for cancers that are positive for estrogen receptor, we treat patients with drugs that block estrogen, and we've seen really dramatic effects and improvement in survival with these drugs. In tumors that over-express the HER2 receptor, we use drugs that block HER2. These have been around since the mid 1990s and have revolutionized treatment for HER2 positive breast cancer. When you look at advances in treatment of breast cancer over the last 20 years, the vast majority of advances have been in ER positive and HER2 disease, but it's in triple-negative where we've had a real challenge. Triple-negative, in my opinion, is really been an awful term to describe these cancers because it's really just a catch all term. It's breast cancers that are negative for ER, negative for PR and negative for HER2, but it doesn't really define what it is. It's in this type of cancer that we're really working hard to identify the best targets to effectively treat this disease.
Aaron: I'm going to ask you a couple more questions about it. If you put in something that blocks these receptors, does it block the receptors on all breast tissue and does that affect the rest of the breast? Or is it because these cancers are just in such overdrive that it affects them more?
Milan: Exactly right. These cancers highly overproduce these targets. So their selectivity of these agents for the cancer cells doesn't mean that these drugs are not without their side effects. We know that ER can be expressed on some normal tissues as well as HER2. But again, because of the high over expression of those receptors on the cancer cells themselves, it tends to be much more selective.
Aaron: Okay. What percent of breast cancers lack all three of these receptors?
Milan: It's roughly between 15% to 20% of breast cancers are triple-negative.
Aaron: When we say triple-negative, if I'm getting what you're saying correctly, all it means is that it doesn't have one of these three receptors and therefore, we can't use one of the other traditional ways that we would treat breast cancer. So we have to think of something else.
Brian: As you think about traditional cancer therapies, I think what many of us revert to mentally is the idea of chemotherapy or, what we call, cytotoxic therapies. These are therapies that really work by non-specifically killing fast-growing cells. So you can imagine in that way, chemotherapies often injure a lot of normal cells. S they have a lot of side effects. So breast cancer has become, I think, the hallmark disease in identifying very early on these over expressed pathways, if you will, or these over express targets, which has allowed us to more efficiently, and I think in a more sophisticated way, attack them so that it really does preferentially kill cancer cells to normal cells.
Aaron: So how do you treat them? What is the best way to treat breast cancer that lacks the usual receptors you might go after?
Brian: Yeah. So as we think about triple-negative breast cancer, historically, this has left us with chemotherapy as the predominant form of therapy. Now, in the last year or so though, there have been a couple of targeted agents specifically for triple-negative breast cancer. One in particular is a use of immunotherapy. As you know, immunotherapy has become an exciting form of therapy across a variety of different tumor types. So there are now two FDA approved immunotherapy drugs, specifically for metastatic triple-negative breast cancer, assuming they harbor a marker to suggest it may work and then even more recently, an antibody drug conjugate. So this is an antibody linked to a poison that targets something seen very commonly in breast cancer, especially triple-negative breast cancer called trop-2, and that drug is called sacituzumab govitecan.
Aaron: So when you talk about immunotherapy, can I get you to just describe what that is exactly?
Milan: Yeah. No, it's been a revolutionary therapy for a variety of cancers, particularly starting in lung and melanoma, but what we've seen is activity across cancer types. When we think about a cancer growing within a resident tissue, one of the things that has to do is it has to develop the ability to evade the immune system. The same immune system that we would normally recognize as killing bacteria or foreign viruses actually has the ability to kill cancer, but cancer has to actually gain the capability of being able to evade it. So in order to evade it, it actually develops a camouflage on its surface, it's called PDL1. This is a protein that tells you immune system to go away. So what immunotherapies do is they're actually antibodies that block that camouflage, re-expose the cancer to the immune system, allowing the immune system to attack the tumor.
Aaron: How do you know if that's going to work?
Milan: That's a million dollar question right there, Aaron, and an area of hot research in breast cancer and other cancers. Who are the patients who really benefit from this type of therapy? Right now, we have early data that tumors that are positive by tissue staining have a preferential predilection to response, but that's still a bit controversial. Truth be told, we lack a very good biomarker for identifying which patients benefit the most from immunotherapy.
Aaron: That's really interesting. So is it just then you just try it out and see who it works on, or are these only being used in studies at this time?
Brian: Specifically, for metastatic triple-negative breast cancer, as Milan mentioned, for those patients who stain a positive, meaning they have a lot of expression of the protein PDL1, there is FDA indication for two different immune based therapies for metastatic triple-negative breast cancer. Now, I think while the studies have definitively shown that the patients who have the staining do seem to respond better or do better, the markers not perfect at all. By that, I mean many patients who have the PDL1 staining don't seem to benefit that much and probably conversely, there are probably patients who are for the PDL1 staining who could benefit. So there's a lot of research going into other markers right now to see if we can better fine tune those patients, things like tumor mutation burden, simply meaning the number of mutations seen in that patient's tumor, and also things like microsatellite instability seem to be markers that predict as well. But again, it's not prime time in my opinion yet.
Aaron: So when you're talking about PDL1, is this something which is also expressed on normal healthy cells, or is this just an adaptation that cancer is developed outside of the normal human system that somehow tricks our immune system?
Milan: No, that's a great question. It can be expressed on normal cells. It's part of our normal biology and what prevents our immune system from attacking our normal tissues. It belongs to a class of proteins. We call it immune checkpoints. There's a variety of these immune checkpoints. Again, it's what keeps us from developing autoimmune disease spontaneously. So PDL1 is expressed on some normal tissues. When patients are administered immunotherapies, the most common side effect are side effects that rev up the immune system against normal tissues. So this includes things like pneumonitis, myocarditis, rheumatoid arthritis, other types of GI side effects. So when patients are administered immunotherapy, close attention is paid to the development of these types of autoimmune side effects.
Aaron: Yeah, because I was just wondering if you give somebody something in which blocks it on cancer, how do we prevent it from blocking it on our cells and then wind up having our body attack ourselves? Are there other sort of more novel ways or new ways that they're trying to find to treat breast cancer that lacks these three receptors besides the ones you've mentioned?
Milan: Yeah, there's really a lot of research in this area. Brian already mentioned we had FDA approval of another drug, sacituzumab, which binds to a receptor present on the majority of triple-negative breast cancers. This particular drug is really neat. It's basically an antibody, a heat seeking missile that has a very toxic payload on it. When that antibody binds that receptor, it gets internalized by the cell, releasing the bomb within the cell and killing the cancer cell. So again, recently, FDA approved for triple-negative breast cancer. A lot of excitement there. Beyond that, we're seeing quite a bit of research in the area of DNA repair, so how our cells repair themselves.
Milan: We know that women who carry the BRCA1 gene, so a gene that predispose them to developing breast and ovarian cancer, if they develop breast cancer, they tend to develop a triple-negative disease. So what we've been able to see through some really neat research from a variety of groups is that if we take women who are BRCA1 mutated and treat them with a drug called a PARP inhibitor, and PARP is a partner of BRCA1, we induce a concept called synthetic lethality. So this is a concept where BRCA1 is like a quality control engineer whose job is to fix DNA. If it's broken, it'll try to rely on this other quality control engineer PARP. If you knock out that quality control engineer, the whole factory goes caput. So the idea here is being able to harness these sort of deficiencies against the disease.
Brian: What's really neat, I think, about that class of drugs is there's a whole cadre of DNA changes in different genes that are kind of similar to BRCA1 and BRCA1, that where these drugs may also be effective. So there's a lot of work now seeing if we can expand the indication for this class of drugs.
Aaron: It strikes me, as we talk about all these things, that they're just so many different treatments. How do you decide who gets what?
Brian: Yeah, this is a great dilemma. As you think, again, even just a few years ago, we didn't really have any targeted therapies for triple-negative breast cancer. What I think you're seeing is a real expansion and we're starting to reap the benefits of a lot of the biology and science that have happened in the past. So right now, obviously, clinical trials dictate how and when we use drugs. As you know, as these new drugs kind of enter the stage as a newcomer, they typically find themselves at the back of the line. But as each of these gains notoriety and benefit, they start to move up and up and up. Certainly, where we ultimately hope these drugs make their way as to the curative setting because in that setting, I think we have a real chance to make major impact and improve curability.
Aaron: But if women come to you and they've been diagnosed with breast cancer, it's triple-negative, it's not responsive, do you take biopsies and run lots of tests on them? How, in the lab, do you decide, "Okay, we've done some test..." I don't know what test, "... and now we've decided this is the therapy we think is best for you"?
Brian: Yeah, this is a great point. Again, in the old days, it was pretty simple. You would test for the estrogen receptor, progesterone receptor and HER2 and make a therapeutic decision. Now, we're seeing an evolution of a number of markers, some of which we didn't even talk about yet, which are markers that transcend all tumor types, but are rare. So to kind of really start tackling that in a iterative fashion, we opened a program here at IU called the Precision Genomics program. This program is really dedicated to really looking across a variety of biomarkers to help sort out which of these may be the most efficient target.
Aaron: Can I get you to talk a little bit more about the DNA therapy? Because I'd like to understand just a little bit better exactly how that works.
Milan: Yeah. No, exactly. I really like where you're going with this, Aaron, because you're really leading into this concept of precision medicine, this idea of tailoring therapy to individual makeup of each patient's tumor. For far too long, we've operated under an antiquated dogma that says, if we take a group of patients with the same diagnosis and treat them all with the same drug, we're going to get the same response, and that's simply not the case. Some patients do well with a particular drug and some don't. So what we challenge ourselves with is using cutting edge technologies, in particular genomic technologies, to guide patients to the right drug for their cancer.
Milan: So in our program, what we're looking for is typos in the DNA blueprint that one, tells us what caused that cancer to go haywire and two, tell us, is there something there that we can block with the drug? And if so, want to be able to guide that patient to that drug that matches their tumor type. So, as Brian mentioned, we started the program in 2014. We've seen over 5000 patients to date across tumor types. It's been really neat because what we've seen over the last several years is just a huge advent of a variety of drugs that have been specifically designed to very particular Achilles heels, particular genomic abnormalities in these tumors, and being able to tailor the therapy to those abnormalities.
Aaron: One of my good friends has developed cancer in the last few years, and one of the things I feel like I've learned this time is just you see cancer, you've seen one case of cancer, that there's still arguments over what kind of cancer he has. It developed in his kidney, but what is it? They're still arguing and I had no idea that was possible. Do you think that this is sort of the future, that we're going to be seeing more and more of a, "We're going to figure out exactly what makes your cancer special and different and find a targeted therapy for that," as opposed to saying, "You have breast cancer or kidney cancer, and therefore, this is what we do"?
Milan: Yeah. I really think that the field is moving to a newer paradigm where we focus more on what makes the cancer tick more than where it came from. Now, don't get me wrong. It's diagnosis is extremely important even to this day in terms of how you use standard of care treatments. However, I think we've gained a real appreciation for this concept of if this tumor has a really unique abnormality that makes it tick, that we can go after it with targeted agents. To that end, in the last two years or so, we've seen the first FDA approved indications for drugs that are pan-cancer that can be used across tumor types if they share a particular genetic abnormality. So I think we're going to continue to see more of that in years to come.
Aaron: Was it more that you think when we have difficult cancers that we'll just wind up sequencing them, logging all the different mutations they have, and then at some point when something comes down, we pull the answer off the shelf and we say, "This is what you do"?
Brian: Yeah. I think there's certainly going to be an inflection point, right? First of all, I think chemotherapy is still will have a role for a long time to come. I think it's been very beneficial for certain subtypes of tumors, but as we get more and more targetable mutations or changes that are able to be attacked by a specific drug and as the number of drugs evolve, there's going to be a point with which genomic sequencing makes sense for every tumor very, very early on.
Aaron: Do you also then just keep the sequencing in a computer somewhere and then go back periodically and check it as more things come down the line? And if so, how often do you go back and check?
Milan: Oh my goodness, we have a huge database [inaudible 00:17:39]. I think it's sitting somewhere at a 500 terabytes of data. So each patient generates somewhere between 100 to 500 gigs of data. So yeah, actually our efforts with the Precision Health Initiative, we developed a partnership with LifeOmic as well, a precision health cloud. It's a database of our genomic sequencing in our patients merged with data from the EMR, both to help facilitate patient care, but also to facilitate research. So this system does, it allows us to be able to interrogate the genome, to identify therapies in clinical trials, and as you mentioned, allows us to even go back to that data at a future time.
Milan: When a patient may need a new therapy or a change in therapy, we can be able to use the system to do that. But even more powerful, I think, is when you aggregate this data. You can imagine what kind of questions you can ask. What are new biomarkers or response? What are new biomarkers of cancer predisposition? What are potential biomarkers is toxicity? So both from the clinical care perspective and the research perspective, having these sorts of computer databases of data are extremely helpful.
Brian: But you asked a really, I think, sophisticated question, which is how often do you go back and when does it make sense to look? Right now, the way we've approached it is when the patient is at a fork in the road, meaning they've had progression of their disease. That's a time when it makes sense to look again because the findings will be applicable, but you can certainly imagine a time in the near future where things like artificial intelligence will really help us to iteratively sort out, "Hey, this patient had a biomarker three years ago. There was a brand new drug that blocks this pathway now. Let's notify all of these patients so they don't get a dropped in the cracks," and I think that's a day we're all excited for.
Aaron: Does this work best for a certain few cancers, or is this something, when you talk about the Precision Health Genomics and Cancer Initiative, is this across all cancers that we're working on these?
Brian: Yeah. So this includes all cancer types. Certainly, we have found that some tumors seem to have more molecular targets than others. Some tumors seem to be driven more by mutational events, whether it be UV sunlight or smoking. Others seem to be very simple tumors. But certainly, we see all tumors and we've been surprised in almost all tumors to find things we maybe didn't expect to find for that specific tumor type.
Aaron: I know you focus on triple-negative breast cancer. Is that because that's just been a particularly hard cancer to treat, or is that because there's something specific about triple-negative breast cancer that lends itself to these kinds of therapies?
Brian: We're passionate about all breast cancer patients and we certainly have been excited to see some of the amazing breakthroughs in all the subtypes, but triple-negative has certainly lent itself well to research and I think certainly lent itself well to research that is focused on genomics because again, this is a tumor type with real mutations and one that I think we need to make major advances in.
Aaron: So while these are amazing, one of the issues that we've talked about across the podcast is that unfortunately, sometimes these kinds of innovations don't get spread equally amongst all people. I know you're also working in some areas that focus on disparities in how women are treated with breast cancer. I was hoping you might talk about that for a bit.
Brian: A few years ago in one of our big Agilent clinical trials, this was a trial named E5103, this was a 5000 patient trial led by my colleague, Kathy Miller, where she was looking at a standard backbone of chemotherapy asking the question, whether a targeted drug, bevacizumab, might improve outcomes. Well, in that trial, the addition of the targeted drug didn't seem to benefit the patients. But one thing that we found, which was really unique, was that African-American patients appeared to have substantially more toxicity from their therapy. What we also found is that they had a higher risk of recurrence of disease.
Brian: Now, that latter finding was not novel. Indeed, other data sets have certainly shown that Black patients have worse outcomes, but it was an interesting finding to see that the patients also experience more global side effects from their therapy. As we dug more deeply into this, what we actually found was that because the patients were having more side effects, they were getting less drug and this was one of the causes for inferior outcomes. This has really prompted us to study this question in a prospective way so that we can start to hopefully, overcome some of the disparities we see in outcomes.
Aaron: What are you actually doing? Are you making sure that doses are kept higher or just following what happens to patients?
Brian: The clinical trial that we initiated to really try to help overcome disparities, especially as it relates to side effects, is a trial with the name EAZ171. This is a clinical trial through the NCI Cooperative Group system. It's enrolling patients all across North America. Interestingly, this is one of the first clinical trials to ever focus enrollment specifically to Black women, again, with the goal of overcoming some of the disparities that we see. So this trial will enroll about 240 Black women across North America. Here, we will follow patients receiving standard therapy. Now, what we found is that one of the taxanes that we use, which is a standard chemotherapy drug, appears to be really well tolerated for white women, but it tends to have a lot more neuropathy for patients of African descent.
Brian: When we talk about neuropathy, this is a side effect that causes numbness, tingling, burning in the fingertips and toes. It's a symptom that diabetic patients often get. Well, it's this side effect that we really wanted to focus on and EAZ171. So here, in addition to the standard paclitaxel, one of the therapeutic options is another drug, which appears to be equally efficacious, but have a lower risk of neuropathy. So in this trial, we're trying to see if we can find a better taxane specific to Black women. What we've also found is that we can predict which African-American women will get neuropathy using their own genetic makeup. So in this clinical trial, we're trying to prove that indeed, we can do that so that we can, again, better counsel patients up front and maybe find which taxane is best for each patient.
Aaron: By looking at their genetics, you can actually figure out which ones will have more side effects to some of the medications you're using?
Brian: Exactly. As you think about the blueprint that makes us up, we are all 99.9% identical. That 0.1% difference is what causes some of us to have blue eyes versus brown eyes, to be tall, short. These same 0.1% differences can impact substantially how we remove drugs from our body and how our tissues accept it. So by focusing on those minor variations, we can really start to sort out which patients are destined to get a side effect from a drug versus those who simply are not.
Aaron: When you sequence to look at all of the stuff you're talking about, I imagine you're getting just... Are you just getting the genetic code, T-A... Well, just a long line and then the computer sit down and crunch and tell you, "Okay. We've detected this sequence, and this sequence is more likely to have worse neuropathy when you use this drug"?
Milan: That's exactly right. What the sequencers do is it takes that long 3.2 billion letter code, chops it into a bunch of small pieces and sequences all those small pieces simultaneously. Then what the computer does is it takes all those small pieces that have been sequenced and stitches them back together, forming the patient's genome. Then what we do from there is the computer starts to look for differences and say, "Okay. Well, what's the changes in the little letter code, that 0.1% that we're seeing across the genome?" Then you take those differences and you begin to interrogate them. You look at the genes that they're present in. You look at their function. You look at what's known about them, and then use that to start predicting your particular phenotype. In this case for Dr. Schneider's neuropathy and our genomics program, it could be a drug target, or it could be predisposition to a disease, or what's really the hot thing, it could be ancestry, determining where your ancestors came from. So it's pretty cool.
Aaron: When you talk about differences though, I'm thinking compared to what? Because are we not all different? How do you know what's normal that to say, "This is the bad one"?
Milan: This is a really evolving area too, and I love how you're bringing these topics up. Currently, the difference is something we call a reference genome. So this is a genome that was stitched together by the NIH many years ago as the comparator. That has worked for a while, but the problem is, is what we're beginning to realize is that, well, that reference genome is not the best. It works, but the reality is there's so much variation in the human population that, that one reference genome just does not cut the mustard when we really need to understand the genome. So what we're seeing right now evolving is this concept of a reference genome that is comprised of hundreds of individuals, uses a comparator, and is a consortium working on this concept of personalized reference genomes, but that's kind of the future.
Brian: But I think important to think about, some of these variants aren't necessarily, "bad," ones, right? So, for instance, the gene that we found important for neuropathy is a gene called SPF2. And importantly, if you were to inherit from mom and dad, this variant, you would have a condition growing up that causes severe neuropathic condition. If though, you inherit only one copy, so from either mom or dad, you have no problems unless you happen to get breast cancer and then get the drug Taxol. In which case, then that becomes a real problem.
Aaron: I just literally am having trouble swallowing the idea that we've got this kind of knowledge for something this, I don't want to say it's esoteric because clearly it's super important, but specific, maybe granular.
Milan: It's interesting. When you read the genomics literature, not cancer, but any of the things, whether it's predisposition to other diseases when it comes to traits, when it comes to personality, it's shocking how hard-coded we really are.
Aaron: So I feel like we've covered so much, but I'd be remiss if I didn't ask, are there any other directions or advances in treatment of triple-negative breast cancer that we should know about?
Brian: One thing that we've been passionate about with all cancer types, but certainly with triple-negative breast cancer is, how can we really move these sort of approaches into an earlier setting, where again, here, the price of making an advance is really increasing the cure rate? One thing that we have found and we know historically is that for early stage triple-negative breast cancer, we often treat patients with chemotherapy prior to surgery. At the time of surgery, about one in three patients will have absolutely no disease left and this is called a pathologic complete response. Importantly, for this third of the population, the cure rate's really good. So about 90% of these patients are cured and good old fashioned chemotherapy is a great therapy. For the other two thirds though, where there is disease left in the surgical specimen, although the disease is all gone, the risk of this coming back and claiming the patient's life is very high. So now, the cure rate plummets from about 90% to about 50%. It's this population where I think we've been really passionate about improving outcomes.
Milan: So as you can imagine, as Dr. Schneider mentioned, now you have a situation where women have been treated with chemotherapy, have gone to surgery, there's still cancer left in the breast at the time of surgery and they're in a really scary situation. They're living really in fear that this cancer is going to come back at any time. We know that about half of these women, their cancer will come back. Unfortunately, when it does come back, it comes back with a vengeance. It typically comes back as metastatic disease, spread to other organs and what we know is that that is lethal. So what we did in a study that we published last July and presented at our national breast cancer conference in December was that if we take a blood sample after surgery and detect for the presence of circulating tumor DNA, or ctDNA, if we see this circulating tumor DNA floating around in the bloodstream, we know those patients are really high risk of their cancer back, almost uniformally.
Milan: However, if they're negative for ctDNA, those patients tend to do really quite well. You can even envision that maybe one day, this is a population that may not need any further therapy and may do well long-term. Based on these results, we are starting a new clinical trial called Persevere, which is going to focus on this ultra high risk population: women who've completed chemotherapy, had residual disease at the time of surgery and are positive for ctDNA. If positive for ctDNA, these women will receive additional therapy, which will be comprised of therapies that are designed specifically to genomic abnormalities in their DNA, combined with the standard of care chemotherapy.
Aaron: Basically, you're saying that this is a way to try to figure out who's at very high risk and then ramp up the other, everything we've already talked about, find them the best therapy that we can really go all out for those who are at highest risk?
Brian: That's exactly right. It's really trying to hone in on those patients where making an advance has an opportunity to really intersect with their destiny and try to improve outcomes, again, using cutting edge tools and cutting edge personalization. But probably equally important, what we really want to do is follow those patients who are ctDNA negative because indeed, if we show that their cure rates are good, our next studies will really be at deescalating or minimizing therapy to improve survivorship, quality of life and all those things that are really important to this population.
Milan: This is really setting the standard of how clinical trials are going to be done in the future in the curative setting, using genomics to guide therapy, to improve cure rate. I think we, as Hoosiers, are really proud that the Indiana University and support through the Precision Health Initiative has really made this happen. This is setting a paradigm, not here in the state, but across the country and across the world. This clinical trial will be open across the country and the excitement for it has been unbelievable, just the sheer number of emails and calls from patients to want to participate. So again, as Hoosiers, I think we have a lot to be proud of.
Aaron: I know you've already been on the show twice, but I feel like I learned so much every time we talk. I hope when you have more advances and things have had gone further and maybe have some results in this, that you'll come back and tell us more.
Milan: Would love to.
Brian: Awesome. Thanks so much for having us.
Aaron: And again, this Healthcare Triage podcast is sponsored by Indiana University School of Medicine, whose mission is to advance health in the state of Indiana and beyond by promoting innovation and excellence in education, research, and patient care. IU School of Medicine is leading Indiana University's first grand challenge, the Precision Health Initiative, with bold goals to cure multiple myeloma, triple-negative breast cancer and childhood sarcoma, and prevent type two diabetes and Alzheimer's disease.