The Changing Landscape of Genetic Testing for Hereditary Cancer with Dr. Jeffrey Weitzel, Vice President of Medical Affairs, Hereditary Cancer at Natera: Audio automatically transcribed by Sonix

The Changing Landscape of Genetic Testing for Hereditary Cancer with Dr. Jeffrey Weitzel, Vice President of Medical Affairs, Hereditary Cancer at Natera: this mp3 audio file was automatically transcribed by Sonix with the best speech-to-text algorithms. This transcript may contain errors.

Saul Marquez:
Hey everybody, Saul Marquez with the Outcomes Rocket, and welcome back to the Natera thought leadership series. Today. I’m super excited to have an amazing guest. We’re going to be covering hereditary cancer and for today we have the amazing Dr. Jeffrey Weitzel. He is the vice president of Medical Affairs, Hereditary Cancer at Natera, he’s board-certified in medical oncology and clinical genetics. Dr. Wietzel pioneered the implementation of genetics and genomics in clinical care, addressing disparities in access and harnessing technical advances to conduct innovative, translational research, spanning the bench, bedside, rare diseases, and diverse populations. He’s, he’s seen it from the beginning to where it is today, and a lot of his work has really revolved around advancing the cause. He’s the founder of Clinical Cancer Genomics Community Research Network, which is a prospective registry with over 30,000 patients, use for gene discovery and validation, innovative translational research, and to assess outcomes of risk assessment for more than 40 sites across the U.S., Latin America. At Natera. Dr. Weitzel is committed to building best-in-class tools for identifying patients at increased cancer risk and for precision prevention. Such a great topic, and I know that a lot of you are going to get a lot out of today. So without further ado, Dr. Weitzel, such a pleasure to have you here!

Jeffrey Weitzel:
Well, thank you, with so many amazings in here, it’s a lot to live up to, but I am excited about the arc of my career and really landing at Natera, where I think a lot of new opportunities arrived.

Saul Marquez:
Agreed. And it’s bringing those opportunities to life and giving, giving the people listening, you know, they’re the patients, they’re, all the things that they’re in charge of, access to, this is what matters. Now, you’ve seen a lot and you’ve seen how this whole business has evolved. What was it like to study cancer genetics in the 80s?

Jeffrey Weitzel:
Well, you know, a lot of it is, I would call it serendipity and opportunity. And for those of us in clinical medicine, you know, so many things influence us. For example, what’s happening when we’re in our training? What’s, what’s topical? What’s, what are the top-level journals showing us? And I thought I was going to be a bone marrow transplanter, I actually went to England and worked at the Royal Postgraduate Medical School in London in preparation for my Hemang Fellowship, which was going to take place in Boston at Tufts-New England Medical Center. And while I was there, I was using the very first forensic DNA probes, so I worked with Sir Alec Jeffreys in Leicester and actually, and a number of other people at the Hammersmith, and I was doing a study of engraftment, but using the first forensic DNA probes, which was, you know, most people don’t realize we take DNA and forensics second hand now, but in those days you had to look at blood types and things like that. So our study looked at ABO matched, sex-matched transplants and looked at engraftment, and published a paper in my first year of fellowship, I got a chance to go to Leicester and meet Dr. Jeffreys, and Professor Jeffreys, and it was really very formative for me because when I got to Tufts, I started working with Ted …, and Ted is an onco-geneticist of sorts, who was really brilliant and was looking at rare alleles of the Harvey Rath locus. Now, today we wouldn’t think anything, we wouldn’t look twice at rare alleles because we know we use them all the time. But in that day it was tougher, but I immediately lined up with that. And what else happened at that time, in 1990, BRCA one was localized to chromosome 17 by Marie Claire King’s Group. She called it BRCA one for breast cancer gene one, but also like to call it Berkeley, California one, because that’s where she was at the time.

Saul Marquez:
Nice.

Jeffrey Weitzel:
But, but the reality is, is that you know, what happens so BRCA one was localized. The p53 gene was linked to a rare syndrome called Leaf Romoney syndrome, all the genes that lead to hereditary colon cancer were all identified while I was at the beginning of my fellowship. And so I, as I say, pivoted or, you know, changed my course and said, this is cool, we need to do hereditary cancer. And we, we have the tools emerging right before our eyes, how to do this so, so really pivoted and started in an era when we didn’t have the same tools. So the other part of this transition as the idea of positional cloning. Today, you want to find it, you want to talk about a gene you just go look it up and you find the sequence and you find out the literature. But in those days, it was basically an unknown, you would start with an anchor, a gene that you knew in this case, the Harvey Raskin on chromosome 11, and we were crawling along 11p, that arm of the chromosome to try and find other nearby genes, basically to solve certain hypotheses. So they call that positional cloning, and I have the great honor of having cloned a gene, which was kind of cool for the time I called it Harvey Rasaplaster one, but we now know it’s actually RASFF seven, which turns out to be an important gene. So it was quite a ride. And my first grant that I ever got as an academician was from the American Cancer Society, a career development award in 1990, and that was to start a familial cancer clinic. And at that point, it was just inspired by what was going on, the tools we might be able to apply, and the ability to start something in a new area. And it really, as I say, the rest is history.

Saul Marquez:
It’s amazing.

Jeffrey Weitzel:
So it was exciting. It’s an exciting time, and there were certain legends, Henry Lynch, you know, I got a chance to meet Henry Lynch. Henry is hereditary colon cancer, hereditary non-polyposis, colon cancer. But he really is, you know, there are several people who we would consider sort of the real leaders, the real inspiring people, and Henry was, he was a tall man, amazing, just amazing. He embraced everybody who would listen to what he started literally in the 60s in terms of talking about hereditary cancer. So, so this is a long legacy, and also, it became clear that the intersection between oncology and genetics was going to be really important. And that was something that I don’t think a lot of people appreciate it and certainly even the clinical genetics community didn’t appreciate. They thought, well, that’s our domain, but immediately oncologists embraced this, and in fact, it was one of those disruptive things, disruptive technologies. Suddenly, oncologists were the ones responsible for cancer genetics, rather than it being the classic clinical geneticists. So I did my next crazy thing, which was I decided to do a fellowship in clinical genetics, which at the time was singular, I was one of the few people in the country to ever do that. And as I like to say, you know, boy, you shouldn’t have to do that just to do cancer genetics, I learned a lot, it was fun. So, so you know, I really, you know, serendipity, and one of my favorite quotes is one from, you know, because I was actually a full-time faculty member in gynecologic oncology, working in medical oncology as well,and running a familial cancer clinic, and I had a KOAT award from the NCI to clone genes on chromosome 11. So you wouldn’t think I had a lot of time to add something, and so I did, I added this fellowship. And you know, as it is, my favorite quote is from Mark Twain I believe, it was attributed to him anywhere, and that’s the harder I work, the luckier I get. And so that is sort of the theme of I think my whole career is hard work, keeping your eyes open and watching where innovation takes us.

Saul Marquez:
Mmhmm. I love it. Yeah, you know what? You said it so well and you were in the thick of it, right? I mean, like it was, it was all unfolding. And today, I mean, in retrospect, it’s all clear. And they’re like, well, yeah, of course, you know, the, of course, Dr. Weitzel’s doing what he’s doing. He’s, you know, he’s an overnight success, no, not really, it unfolded slowly. And so, as you reflect on a lot of the developments that have happened, what would you say are the, are some of the hallmark developments that you’ve seen in cancer genetics through your career?

Jeffrey Weitzel:
Yeah. Well, I think, you know, certainly.

Saul Marquez:
You mentioned a few of them already, but, you know, just curious.

Jeffrey Weitzel:
But they are actually important because, for example, when you talk about hereditary cancer or even these very niche sort of settings, so the leap from any syndrome was, you know, you can almost count the number of patients on a couple of hands at the first outset, even though it was an incredibly important syndrome, a p-gene, p53, and all of these other things. But I think BRCA one and BRCA two subsequently because they were, you know, they really spawned the genetic testing industry in the sense that there was what I like to call an academic industrial collaboration, which is was ultimately eventuated in myriad genetics and their patent position, but they were collaborating with academicians. And what did they bring to the table? Just brought a room full of sequencers. And so that technological brute force approach yielded BRCA one, and commercial testing first became available broadly, I’ll say, in 1996 and what have we face at that point? Well, new test it wasn’t in the usual test roster, one exclusive provider, so we ended up having all of these implementation challenges, which related to insurability, this is research, right? So the classic line from insurance companies is always it’s research. Well, no, it wasn’t, there was serious disease behind this, this is also not a trivial gene, you know? So it really gave us the exemplar of what I call high penetrance or high risk genes that make a huge impact on the individuals and their families, and there were already some interventions because the clinical picture had been, around for a long time, it’s just that people had to do it on their own. In other words, people had to make things work because of family history. So people have done mastectomies, for example, for family history of breast cancer for decades, but the question was, were you really at risk? And here you had the opportunity to decide, did this person have the same predisposition, would they be relegated to average risk? Or should they in fact have this knowledge that empowers them to choose their draconian interventions at that point, removal of certain tissue, you know, in a wise way. And so the potential power of this approach, this informed approach, was really quite apparent, especially to the oncologists who dealt with this on a daily basis in their clinics. So, so I think that that was one of the seminal things that really seeded the genetic testing industry. And even today, it’s still, probably two thirds of the business is women and risk for breast and ovarian cancer. The other thing is that it was already audience, these women take care of families and people, they drag their husbands in by the year or their kids in by, you know, to get them engaged. So people who are caretakers, who take care of families, genetics is a natural field. The natural, you know, caters to them. It’s, in fact it’s the truest form of primary care or family medicine, in my mind, is really genetics in a big way.

Saul Marquez:
Yeah. Data-driven primary care. And so you’ve trained thousands of clinicians in the U.S. and Latin America, and you’re a household name to genetic counselors, what do you love most about teaching?

Jeffrey Weitzel:
Well, you know, teaching is paying it forward. You know, first off, it gets you the opportunity to talk about things that you are, you know, you’re immersed. So I think part of it is, you know, if you’re in this milieu, you want everybody to know, you’re excited, you want everybody to know why you’re excited. And the other thing is that you know, what’s now matured into a science of its own is something called dissemination and implementation. So you have things that are going to make a huge impact on people, in fact, and when I think about BRCA one, I’m just going to segue way back to that for just a moment. I’m proud of the fact that we figured out how to do BRCA one and BRCA two testing, then for more than a decade, that’s all we had at the high level of commercial testing. Lynch syndrome came along, we were able to start doing those genes as well, and that was added. But the reality is, is that that was really the exemplar. But what I’m most proud about isn’t even that we could do genetic testing, is that we did the clinical work to discover what’s the evidence for the outcome, how do we prevent those cancers? And so we have a rich evidence base now that drives the care of those individuals. And so we know that if they do certain things like removal of the tubes and ovaries for prevention, that not only is that going to eliminate their ovarian cancer risk, but it’s going to reduce their breast cancer risk. So we have this rich evidence base now, and that’s really what was the hard work is providing the evidence for our advice. But, any then, having said that then, then the next step is, well, the genetics we learned in medical school, boy, that fades pretty fast. You know, I have an anecdote that I didn’t know I was going to get into genetics until much later, but my genetics professor in medical school was Dr. …. There’s a syndrome named after him, and he was the most amazing teacher, so you asked him about teaching … was the most amazing teacher. He would do the Oprah thing, he’d be stroked, striding up and down the proscenium, and he must have known, I’m sure he actually studied our class picture, so we had two hundred and forty kids in the phase eight classroom in genetics, and he would stride up and long, and he would call Carla Grossman, one eight, two N’s, 15 rows up, and she’s looking around like, who’s pointing at me? You know, so he put people on point and sort of the Socratic method of teaching, and it was wonderful, you are on the edge of your seat. The other thing about teaching is you have to be a good storyteller, you need to engage your audience. If you’re just droning on about clinical studies, you have to add a personal story to it, you have to give it a face or at Natera like we say, there’s a patient behind every test. So I think that this is something we really believe in, that the stories have to be there, so part of implementation is we realized very quickly and this was an important task for ASCO, my colleagues, Ken Offit and other people, I really consider Judy Garber, Fumiola Paty, these are all leaders in clinical cancer genetics, they’re all oncologists, and we recognized right away that there was a knowledge deficit among oncologists. And yet they were the ones who are seeing the patients affected with these diseases, and they would be the point of the spear in terms of getting people tested. And so ASCO started educational endeavors. We, I was a participant in those early days, we did train the trainers. You had to figure out how to scale up and that really was a seed of my own real inspiration to continue an education because without education, you can’t implement and if you can’t implement your all losing out on access to life saving opportunities. So, so I think it’s about responsible integration of these new technologies and education became the means to that, so that, that’s really it. And like I said, the idea that this is a way to pay it forward, I can learn how to do something in my own practice, but if I can influence 20 practices and they in turn train their fellows and their residents, create curricula that are durable and disseminate, yeah, you know, you make a much larger impact, and that’s what it’s about. That’s the point.

Saul Marquez:
Yeah.

Jeffrey Weitzel:
It’s amplifying that. So that’s why education and for some, I think it’s more natural than for others, but I don’t mind being on the podium.

Saul Marquez:
I think that’s great, and it’s a very insightful way to look at it, not only from a, you know, knowledge dissemination perspective, but also from a commercial perspective and an access perspective, it’s critical. So as you think about some of the key ways patients with cancer can benefit from precision medicine, which ones would you outline here for us as as a good takeaway lesson?

Jeffrey Weitzel:
Well, I think, you know, for for patients, it’s really understanding what they can do to prevent cancer. I mean, I think where I’m really excited is and the whole field is going really is toward something I’m going to call precision prevention. I’m not the first one to coined that term, talking about precision medicine, but there are some famous quotes actually back to the 18th century that to prevention is so much better than treatment because it’s bears that bearer the burden of having had the disease. So, so it really is a different way, and it points to the importance of survival. The other aspect of this is when you talk about testing, we used to focus almost only on testing those people who had cancer where you’re interested in explaining, and we now have evidence for the advice and this need for something we call cascade testing. So cascade is when you find something in the family making sure everyone in that family whose blood relative has the chance to find out whether they’re a carrier or not. And that’s where real true prevention and cost effectiveness of survivorship really takes hold. And I got to tell you, there’s nothing more potent than, you know, even though I would have women with metastatic breast cancer in my clinic and dealing with all of that, the death of dying, all of the aspects of the emotional support in that setting, but still almost to a person, they were worried about their daughter, they were worried about their sisters, you know, I want to make sure that nobody else in my family suffers this outcome. So really, this is responding to patient’s needs, to what they value. And so really the patientcentered approach, the value added and making sure they get good advice for what’s found in the genetics realm, those have been basically part of a mission for me, for my lifetime.

Saul Marquez:
Yeah, I think that’s great and this idea of precision prevention, you know, and folks, you’re listening to this right now, think to yourself, what can you do in your care areas to introduce or scale precision prevention? And to that end, Dr. Weitzel, what advice would you give to, you know, a large system CIO or a chief medical officer that’s trying to make this happen, you know, at larger scale?

Jeffrey Weitzel:
Yeah. So, you know, one of the things I’d point out, which is interesting, it turns out that even though pharmaceutical companies are not so interested in prevention, necessarily, right? They treat diseases.

Saul Marquez:
Right.

Jeffrey Weitzel:
So so I can actually count the number of drugs that have been approved for prevention of cancer. Almost on one hand, you know, among them is, for example, tamoxifen, is generic. Who wants to develop that from a cost perspective, it’s like $30 a month at the generic rate, and yet it can reduce by 50 percent ER positive breast cancer among women at risk. So, so I think we really need to get people hear, but the point is is that prevention is more economical than treatment. I’ll give you the example of ovarian cancer if we identify those at risk for ovarian cancer and there’s wonderful genetic tools, the NCCN guideline, which I was on the committee for 19 years representing the City of Hope, is that, you know, they, all ovarian cancer patients need to be tested, and why? Because it turns out that we can prevent that disease, and with relatively low impact and low morbidity, it costs over $100.000 to treat one ovarian cancer. And so whatever the cost of screening one hundred people, I just saved all of that by doing, you know, identifying one or two and preventing that. So when you think systemwide, prevention is cost effective, I’m glad to see that many CIOs and others are doing things like incentivizing exercise, good health habits, things like that So, so I think that genetics has the opportunity, also, I think patients and families would believe it to be a good benefit if you’re doing it for employee systems, things like that. But I do think that prevention needs a place at the table and it goes beyond cancer, frankly, you know, when you think about optimizing cardiac risk, and it turns out that there’s things that overlap in my more recent research in clonal hematopoietic system, things that are really fascinating about the intersection of inflammation, the inflammasome and cancer risk and other chronic disease risk. But ultimately, I think that it’s an opportunity, it’s a good benefit, it’s not as expensive as it would seem on the surface, especially when you only have to spend that once and that the investment in prevention pays you back many times over.

Saul Marquez:
Yeah, yeah. And you know, it’s interesting that you mentioned Kaiser, I think being a vertically integrated, you know, payer provider system, it’s also, they’ve got to keep their their eye on, on those dollars, employers too, right? I mean, employers could highly benefit from giving this as a benefit to their employees.

Jeffrey Weitzel:
Yeah, I think so. And, but I think also it’s getting implementation across the entire arc of health care. And, and I think, you know, Natera at this point is, you know, obviously been focused and had such immense virtuosity in the women’s health space when thinking about people innovation that in fact, what’s one of the biggest, coolest innovations coming out down the pike, it’s multi-cancer detection using cell-free DNA. This is a whole technological thing, but people don’t realize is that that actually came from non-invasive prenatal testing. They were doing cell free DNA, they’re the ones who mastered that space, they found there were a few cases where a pregnant woman had an abnormal pattern on the NIPT, but it wasn’t a baby, it was actually a cancer. And so, you know, to me, that was almost a decade ago, I had, the light bulb went off in my head that this was going to be exciting and a lot has grown up around that. So, so I think that they’ve been innovative. They’ve also come along at a time when we’ve recognized that, now that we have this vast evidence base for how to take care of people if they have high risk, particularly for breast and ovarian cancer and for women at risk and then think lynch syndrome and the uterus, there’s there’s all kinds of applications. The fact is, is that implementation is lagged. Clinicians will say, I’m so busy, I only have five minutes to add something new, so you need good product support, you need people who can stand up a good counseling system so that patients can get quality counseling and genetic education, while at the same time getting access to testing. And we’re not quite at a population-based approach that is just test all comers, but it’s getting closer. So if you’re one step removed from those cancers, it’s now part of the NCCN guideline to be able to get access to that care. And again, it’s what we get into prevention, so

Jeffrey Weitzel:
I’m also interested in disparities and global health, so we created educational tools to really bring training expertise to clinicians in community settings, which is really the whole idea of the dissemination implementation. We’ve been doing commercial supported testing for BRCA one and two since 1996, so almost 25 years, yet majority of the developing world and other nations actually don’t even have access yet for their public health population. So, you know, we created an implementation project which we call Gracias, which involved training clinicians in Peru, Colombia and Mexico, and then in my laboratory, I was providing genetic testing at not the most innovative, just the cheapest, I could do a whole panel for seventy dollars. Now, we implemented this, tested more than 5,000 people in that setting and created access to care by training clinicians, building infrastructure and getting ready to do this. So I think there are disparities globally the cost of the testing, even though it’s coming down a lot because of next generation or subsequent generation technologies, it’s still probably a lot of value, too much for broad implementation for populations, but again, prevention is so much better than cure, it spares the laborer from being sick and it ultimately we have to have our cost effectiveness model arguments. That reality is that if I screen for ovarian cancer and if I prevent even one, I’ve just taken care of hundreds of patients in terms of that cost benefit ratio, to say nothing of improved life mothers who are around longer for their families.

Saul Marquez:
Oh my gosh, yeah.

Jeffrey Weitzel:
So you know, it’s getting that message out and understanding that, yeah, that seems like, sort, we’ve got to get beyond short term thinking in terms of profitability and look at long, long game. How are we going to maintain survivorship and well-being for our families and our friends?

Saul Marquez:
Yeah, and your passion is palpable, and I just love the way that you speak about this, it’s definitely wonderful to have somebody like you in a position that, that you’re in, with the influence Natera has in the market. Why did you choose Natera? And then what are you hoping to bring to Natera’s Hereditary cancer and oncology programs?

Jeffrey Weitzel:
Well, it’s a great, great question because, you know, it was a significant pivot in my career. So, you know, you go not as far as you can. There’s certainly more I could have done in the academic setting that I was in, but the reality is is that I saw Natera as an up and coming company. They had already done tremendous work in the women’s health space and really, again, the virtuosity, the nimbleness of the company that really impressed me and they courted me because they had a new test in power, their hereditary cancer test. And I thought, well, natural evolution of where you should be going, they need to implement that, I want to make sure that it’s the best test around, that’s bulletproof, that it provides really the most advanced hereditary cancer testing possible. But what really the other aspects of this was they were positioned well, nationally and internationally, so I can make an impact if I can improve a product and make access to it and assure quality counseling and education services for patients. You know, they have this mantra that you know, there’s a patient behind every test. Ok, well, that aligns well with my values in terms of quality, and it’s about the patient, not about anything, you know, other than that. And so they are innovators in this space, they were nimble, and so if I’m going to influence an industry standard bearer, at least I felt that there was a place that I could make a difference. And in the near term, not in the long term. You know, I want to be able to change the face of this and they’re innovating in multiple other spaces. So, you know, you take non-invasive prenatal testing, you add in their sign Natera, so their bespoke assay for minimal residual disease, already, I look at this and go, oh my god! In colon cancer, this could supplant CEA testing, which has been arcane for so long, yet this really opens up a lot of new vistas. So there’s exciting things happening in multiple business units, and I view my role as one of transcending those business units. I’m actually situated in their women’s health setting, but I’m an oncologist and geneticist, so I want to bring to the oncology side of that shop what women’s health has been doing and vice versa. And there’s so much synergy that can happen there. Plus there are other innovations in areas that are under development. I know it’s publicly available knowledge that they’ve created a new business unit to look at multi-cancer detection, for example. So, so I looked at this as all of these tools I’m interested in for precision prevention, well, we’re building them and we’re going to deploy them. So we’re going to identify those that make it accessible, identify those are at risk, make sure they’re are counseled adequately and hopefully be providing some of the best tools in class for helping preventing those cancers or early detection, and then precision therapy, right? So already identification of genes. So this whole, call it the marriage of the tumor and the germline, that’s a whole nother thing. There’s 50 ways to find inherited cancer through all the oncology space of precision medicine, so I’m excited about being in a place that innovates and that has demonstrated an ear to what I have to preach.

Saul Marquez:
Well, I would certainly agree and really want to say thank you, Dr. Weitzel for today, all of the history, the, the nuances and the opportunity that we have to take advantage of the work that you’re doing there, as well as what Natera is doing to prevent the preventable. Just want to give you a big thanks for joining us today.

Jeffrey Weitzel:
Oh my pleasure and thank you for having me! And if your audience has questions, certainly reach out.

Sonix is the world’s most advanced automated transcription, translation, and subtitling platform. Fast, accurate, and affordable.

Automatically convert your mp3 files to text (txt file), Microsoft Word (docx file), and SubRip Subtitle (srt file) in minutes.

Sonix has many features that you’d love including secure transcription and file storage, automated translation, automated transcription, share transcripts, and easily transcribe your Zoom meetings. Try Sonix for free today.