Speaking of Women's Health
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Speaking of Women's Health
From genes to guidance: How ctDNA and MRD shape treatment choices
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A drop of blood can change the course of cancer care. Speaking of Women's Health Podcast host Holly Thacker, MD sits down with variant curator Stetson Thacker, PhD to unpack how circulating tumor DNA and tumor‑informed minimal residual disease testing help clinicians see recurrence months before imaging, tailor adjuvant therapy, and track response in real time. Together, they translate complex genomics into clear choices: when a negative MRD result supports de‑escalation, when a persistent positive argues for chemotherapy and how colorectal and breast cancers have led the way in clinical validation.
They also cover the guardrails. Not everyone has banked tissue for a tumor‑informed assay, and sensitivity and specificity vary by platform and cancer type. Early multi‑cancer detection tests promise a lot but risk overdiagnosis and anxiety if used without clear indications. The smarter path is matching the right test to the right person at the right time, ideally within guidelines and with an oncologist who can synthesize genomics, imaging, pathology, and patient goals. From colorectal screening shifts to balancing overtreatment in prostate and thyroid cancers, we focus on practical decisions that protect both survival and quality of life.
If this deep dive helped you make sense of liquid biopsies and MRD, subscribe, share the episode with someone navigating cancer decisions and leave a review so more listeners can find the show.
Meet The Guest And His Role
Dr. \Welcome to the studio women's health podcast. I'm your host, Dr. Holly Backer, and I am back in the Sunflower House for a new episode with a very special guest, and that is Dr. Setson Backer. No relation to me at all. I always say that, even though I know the audience knows that he's my oldest son, and he's very popular because he he's a lot of people ask me to have him back on. He was on in season two and three, and we talked about anti-aging strategies and genetic testing. So we are going to talk and dive into the fascinating world of circulating tumor and DNA testing for minimal residual disease. But before we get into this leading edge and fascinating topic, I want to go over a little bit about Dr. Backer's impressive background. Stetson graduated from Denison University with high honors and a bachelor's degrees in biology and English literature. And he received or earned his PhD in genomic and molecular medicine from Case Western Reserve University. Stetson works at Netera and he is a variant curator. Welcome, Stetson. Tell us what a variant curator is. That's kind of a mouthful, just like the topic we're talking about.
SPEAKER_01It is. It's a bit of a newer profession or or job that's that's out there since the blossoming of genetic diagnostics. So it's, you know, there's been a major advances in producing DNA data, but the big question is what does it mean? And the variant curator is sitting in that phase of things and figuring out what the results of a DNA diagnostic test mean. Because you can change many different things across a gene. They can change in many different ways, and the consequences of those changes are not always clear. And so the role is to understand whether the changes are clinically meaningful or not. And there's many, many different protocols and processes and tools that go into figuring that out.
Dr. \So let's just first talk about why our audience or anyone listening would be interested in having a better genetic kind of or genomic imprint of tumors and cancer, and why cancer is important, and why is it rising in frequency in certain groups and in certain people.
SPEAKER_01So there's a hot term in oncology, cancer care, personalized medicine, and precision medicine. And that paradigm or that that vision of delivering medical care in a in a personalized or more precise way is most mature in cancer, in the cancer field, and it's most mature there because of the technology that we have to look at the genomes of cancers. Because every cancer is unique in its own way. They carry changes to the genome of that cancer, and the cancer itself has different genomes throughout it, because cancer functions like a tissue in many ways. And so this precision oncology, this this vision of personalized care is really why we're interested in learning about the DNA of cancer. And there's many different ways it can be meaningful to the care of cancer. It could be valuable in the treatment. There are certain drugs that are specific to certain changes to the DNA of cancer, but there's other ways it can be meaningful too, in terms of identifying how likely the cancer is to be aggressive or not aggressive, or also just for other uses, which we'll talk about today in terms of following or surveilling or assessing the risk of recurrence or assessing the effectiveness of a treatment in real time.
Updating Germline Testing And Panels
Dr. \Well, that certainly sounds to be so important, and the patients certainly that I see are always interested in individualized care. They don't want one size fits all. And when I did my training in medical school and residency, and I rotated on the so-called liquid wards or the solid wards, which are two different ways of describing clinical cancers, either of the blood system or of solid tumors, it seemed almost barbaric some of the therapies in terms of chemotherapy that just kind of kills all cells, even the good cells, the hair cells, the stomach cells. Terrible vomiting. And to see the evolution and undergoing chemotherapy and radiation is so much more targeted and precise, and there's better treatments for the side effects and more focus. It's really just, you know, exploded during my career. And in season three, we had an interesting podcast with Dr. Corrine Men, who was diagnosed with breast cancer in her 20s when she was an OBGYN resident and had negative genetic testing. And then later on, she demanded to be tested again, and she had a variant in the Bracogene in the larger region and got treatment. Anyway, became a mother, finished her residencies, practicing, you know, 20 plus years later. So hopefully cancer doesn't have to be as scary a term. It's not a death sentence. And the sooner we can pick it up, the more precise we can treat it, the better people feel and fare. And since it is one of the more common causes of death and does increase with age, and we're seeing higher rates in younger people. I wonder if you had any any comments about that.
SPEAKER_01So I think there is uh new analyses that come out, and I don't think there's any enormous increases among younger people. Their exception is perhaps colorectal cancer among among young people, and that's really kind of the only only real space where perhaps is increasing among younger and younger people, so far as I know. I haven't given a really close look at that, but yeah, so I don't think there's really any concern that there's some sort of epidemic of young adult cancer, and it's most likely that cancer that onsets early in life has some sort of hereditary component, whether that's because an inherited germline variant or some early somatic change that's that's driving the cancer.
Dr. \Well, we've been noticing this about colorectal cancer. In fact, I revised just the other day some of my patient education information because we don't just do routine screening at age 50 like we did for several years. I mean, certain groups, family history, African American, we would maybe start at 45, but now we're starting at 45 for everyone, and sooner if there's a family history. With the breast cancer uh germline genetic testing, we know to recheck it if someone has been tested before the fall of 2013. Is that true for other cancer panels? Like if someone had colorectal cancer, like I have patients who had colorectal cancer when they were pretty young, they went for testing, they didn't have lynch or other known mutations, and they were told that's it. I mean, are those people that we should be sending back for repeat testing now that things keep evolving in this field?
SPEAKER_01It's a complicated question. It may depend on the case-by-case situation, uh, especially if there's a potential for there to be risk in other first-degree relatives in the family. Yeah. I think that that creates like a potential greater urgency to pursue additional testing. But it is true that the genetic diagnostics that we have today are much more advanced than we had even in the recent past, and there's they're continuing to advance, and we continue to learn new things. New risk loci for specific cancers are discovered. One would think that we almost know everything there is to know, but it's that's not the case at all. We we discover new things in genetics fairly regularly, and so there could be a very real clinical reason to do an additional test in some way. And now increasingly we see the use of whole exome and whole genome sequencing in clinical settings as well, because it's possible that someone has a totally never-before-seen variant that is causing the disease that they have, and that the only way to really identify it would not be using any panel because it's it's totally new and it's in some place where we don't think to check. And so the real way to find it may just be using one of those comprehensive tools.
Exome Sequencing Explained
Dr. \And go into a little more detail about what whole exon uh sequencing is.
What ctDNA Is And Why It’s Hard
SPEAKER_01So the exome that just refers to the segments, the parts of the genome that code for proteins. The typical biology 101 or genetics 101 lecture is that a gene codes for a single protein. Now, there's a lot more complexity in there, but the parts of a gene that code for a protein are called exons, and they're interspersed by things called introns, which don't code for protein. That's why we have these different terms for it. And so we have a way of just capturing the exon part of the genome, the part that codes for the protein, and sequencing those regions because those are functional, we know those are functional regions. There are other functional regions in the genome, but we don't understand them as well as we do the exome, because we we know they make proteins and we know a lot about what proteins are doing in the body. So we look for the regions that code for protein for mutations that would change the function. And typically we're looking for mutations that are causing a loss of function, meaning they disrupt the way the protein works, whether it's totally destroying it, keeping it from folding into its important three-dimensional shape and doing the function that it does in the cell, or it's just uh totally obliterating any production from the gene at all. Some loss of function mutations cause something called nonsense-mediated decay, and that means the gene is not even turned into RNA. There's typically a it goes from DNA to RNA to protein, and that step where it's supposed to make RNA is disrupted by certain mutations.
Dr. \Now tell us what a circulating tumor DNA or CT DNA test is.
SPEAKER_01So the idea behind circulating tumor DNA is that in your body, if you have cancer, or this this can be for detecting fetal DNA too in maternal circulation. So there's other possibilities that you're looking for other circulating DNA. But typically when we say CT DNA, that's circulating tumor DNA. And so tumors in your body, they undergo some cell death. And when those cancer cells die, they shed some of their DNA. And as we mentioned before, cancer genomes have mutations that are distinctive, even individualized. They're unique to the person. And so the idea behind finding circulating tumor DNA is to use a blood draw, pull out the blood, and do you apply the DNA sequencing technology to find the little fragments of circulating tumor DNA that are in there with all the other normal healthy DNA that's circulating in your blood, too, and detecting it with that DNA sequencing technology. So it is kind of like finding a needle in the haystack because, in terms of like what how many parts of tumor DNA are there versus how many parts of healthy DNA in there, it's you can be as small as like one to one hundred thousand or even more. That is that can be a real struggle. So you need a really sensitive or really specific assay to detect circulating tumor DNA.
Dr. \And what is minimal residual disease or mRDNA?
SPEAKER_01And so the top-of-the-line c DNA testing, or what's typically the most clinically valuable, is using testing for CT DNA to understand if there is minimal residual disease. And that just refers to the small bits of residual cancer that are in the body after treatment has been administered. And that these this is a type of minimal level of disease that cannot be detected with standard imaging techniques or even other molecular approaches. And so using tumor DNA, finding that tumor DNA in circulation is really the most sensitive and specific way to get at the question of whether there is some residual disease after you've been treated, after it's been surgically removed or after you've been treated with chemotherapy or in radiation.
Dr. \So I think a lot of cancer survivors are used to having to go back for their repeat chest x-ray or repeat CAT scan or repeat PET scan, which does involve, of course, especially with CT scanning or fluoroscopy, you know, a lot of radiation potentially. So this sounds like it's so much more precise and finds it so much earlier and doesn't involve the imaging. But from my perspective as a clinician, um and from the understanding that you know we can make abnormal cells or cancer cells regularly that our immune system takes care of. And certainly there's some cancers where early detection makes a huge difference, like in cervical cancer, skin cancer, colon cancer. But in other cancers, particularly in older persons, particularly breast and prostate, if you do screening tests or biopsies, you can find cancer, but is it clinically relevant? Is it a false positive? Is it something that's biologically active? So does this MRD is that helpful in terms of determining that?
Imaging Versus MRD: What Changes
SPEAKER_01So this it's MRD would be distinct from that issue because disease has already been established in individuals who are being pursued for MRD testing. They've already had a diagnosed cancer. They have, whether it's early stage or late stage disease, it's already well known that they have the disease. So it's not a diagnostic test in terms of do you or do you not have cancer. Now you can use these tests, they call it something else. It's not MRD testing, it's called multi-cancer early detection tests. And there are some of those that are already in the market now where it does raise those questions. Like, is the positive on the multi-cancer early detection finding circulating tumor DNA actually finding real cancer or clinically relevant cancer in the body? And so that is an important question when using the technology in that way. But that's not a question that arises with MRD testing because we're already 100% confident that this individual has cancer. Other the question is whether this, whether the residual cancer is clinically meaningful or not. So that's the question. Is it pop positive or if you pop negative on an MRD test? Is that clinically meaningful? And there has been a lot of research that when you do this, you are getting a real clinical signal. The other thing that is special about MRD testing, now you can do it in two different ways, is that you're using information from the original tumor. So they you take DNA from the original tumor, you take DNA from healthy tissue, and you create a profile. It's a bespoke profile using a set of markers that this is the signature of your cancer. And then you do biopsies of the blood looking for the signature in circulation. And so there's been, of course, validation work that when you do this quote, tumor-informed MRD testing, that you can get clinically valuable information. Now there's even different ways that it can be clinically valuable. But one of the main ways, of course, is prognosis. So if you have you've been treated for your cancer, it looks like you're disease-free, they do the liquid biopsy, just mean, which just means a blood draw. They do the blood draw and they look for this MRD. If you're MRD positive, that's not good. Versus if you're MRD negative, that's a better sign. If you're MRD negative again, three months, six months later, that's an even better sign. Right.
Dr. \And does that allow the physician and patient to maybe forego all this imaging with radiation?
Using MRD For Adjuvant Decisions
SPEAKER_01So I don't necessarily think of it as a replacement for imaging. I think they'll still want to do the imaging on the patient as well at whatever the regular periodic exam that had been established in the practice guidelines previously for whatever the cancer that we're talking about. So they'll still do the imaging, but it could be informative of when you need to stop treatment. And so that's the other thing. There's a big question about after it seems like you've removed all the cancer, say it was early stage disease, and say you're even a young person, and you have an option. Should you get chemotherapy or not? It looks like your cancer is gone. Do we need to treat you with chemotherapy or not? You you're young, you want to be aggressive because you don't want that cancer to come back. Recurrence is bad, that could dramatically shorten your life. So you don't want, but you also don't necessarily want to incur the side effects of getting that chemotherapy because it could you know forever infect your quality of life as well. And so using an MRD test could help resolve that question in certain instances. So you could do a tumor-informed MRD test, like Netera offers with Cignatera, and if it's positive, it may be worth considering adjuvant chemotherapy. And then you can also follow your response to that adjuvant chemotherapy over time. Does the MRD testing turn from positive to negative, for example? And so it's allowing you to follow the treatment in real time as well as make decisions about whether or not adjuvant chemotherapy is a worthwhile decision to make.
When Oncologists Order MRD And Benefits
Dr. \Well, anything that helps to clarify that role, I think, is a very big advance. And you've been listening to this podcast. I'm your host, Dr. Holly Thacker, and we have guests Dr. Sesson Thacker in the Sunflower House talking about circulating tumors DNA and looking for residual disease and indications that have cancer. So, why would a patient's cancer uh physician order this test and how does it work and what are the benefits?
Tumor Profiling, Oncotype, And CGP
SPEAKER_01So we've touched on some of these already. A lot of times a patient may have been successfully undergone surgical resection, and there's a lot of options that are available for the patient after this, like we were talking about. They could choose to get adjuvant therapy, they could, they could just be up for active monitoring, many number of things. And so that's where this MRD testing becomes extremely useful. You could also just want to use it to assess is also what what is the risk of recurrence, and you're you're finding out earlier rather than later, because you'd still be checking for it in the patient, but you may find out six to twelve months earlier if you're using the CT DNA test for MRD versus waiting for your regularly scheduled imaging test. Because the only tests only finds the metastasis or regrowth of the cancer when it's reached a certain size. Yeah. And so it's less sensitive. We're talking like in terms of like millions of more cells versus in terms of when the test can detect the cancer is there or not. And so, yeah, that's why it's it's so valuable and why it's increasingly used. But it's really demonstrated the most benefit in colorectal cancer and then breast cancer after that. But we continue to do clinical research in other setting after other setting. And there's obviously complications between doing this for a solid tumor where it's more applicable versus doing it in a liquid tumor. Because obviously, when you have a liquid tumor, the cancer cells are already they're in the blood, they're circulating in the blood, and they're not in one specific place.
Dr. \Now, a lot of cancer patients are used to getting genetic testing on the tumor itself, which is different than the germline, testing for inherited risk or various mutations of high penetrance, medium penetrance, or low penetrance for cancers like oncotype DX. Is that at all related to the signature of the tumor, or that's just another way of assessing the aggressiveness of the tumor and the need for aggressive treatment?
Targeted Drugs And Immunotherapy Gains
SPEAKER_01Yeah, so that's that's just another way of doing personalized cancer genetics or precision oncology. And so what you're mentioned, you mentioned two different things actually. You mentioned the oncotype DX test, which is uh another way of trying to assess prognostic factors. I think that you know it's used in breast cancer. There's also one in prostate cancer, I believe, and maybe some other ones. And so that that actually looks at RNA expression rather than DNA, I believe. And so it's looking at the expression of several RNA genes, you know, psoa genes expressed to RNA. So it's looking at the expression of certain genes, and those genes are said to be predictive of whether the cancer is going to be more aggressive or not. So that's that's one example. So it's it's a different way of getting prognostic information on the cancer. So that could be complementary to something like MRD testing. And then you also mention what we call uh comprehensive genomic profiling or CGP of the somatic cancer genome. And that can be done for a lot of the times it's done to try to understand what therapeutic approaches should be used for the cancer. And so that's especially useful in lung cancer, for example, where there are nine different genetic biomarkers that can be informative when determining how to treat the lung cancer. For example, there's A gene called EGFR. And EGFR can be commonly mutated in certain lung cancers, non-small cell lung cancer, and there are many different drugs available that inhibit the function of EGFR because the EGFR mutations in lung cancer oftentimes make that gene go crazy in terms of its activity, and you want to stop that activity because that activity is helping the cancer grow. And so if you have that specific mutation, you can use these specific drugs to target that. And there's many examples of that in lung cancer. You can also understand how much of a what we call tumor mutational burden exists in the somatic cancer. And if you have a cancer that has a high tumor mutational burden, that sometimes or can often make you a good candidate for immunotherapy drugs. And there's some remarkable responses to immunotherapy drugs. So it's always a good idea to find out if you're eligible for those types of drugs. And that's why comprehensive genomic profiling can be very valuable.
Dr. \And is that some of the reason why we've seen such improvements in disease-free intervals with cancers that in the past were really like very bad prognoses like lung cancer and melanoma?
SPEAKER_01Yes, yes. So I think, especially in the melanoma setting that you've mentioned, I think we've seen a lot of benefits in terms of overall survival or just disease-free survival windows because of the application of those immunotherapy drugs like Pamproluzimab, Nivolimab, Epilomab, those those sites, those kinds of drugs have shown really remarkable benefits in in those sorts of settings.
Dr. \And knowing if a patient has a germline mutation also can help in terms of selecting specific anti-cancer drugs as well, correct?
Limits Of ctDNA And Access
SPEAKER_01Yes, yeah. It could, it's not necessarily just the somatic mutation. Sometimes a germline mutation can matter a lot too. Um trying to I think the PARP inhibitors are one example of that with bracket mutations. There's there's a little bit more of the debate about what setting do PARP inhibitors work best in, or what is the clinical benefit of PARP inhibitors, but that is an example of a treatment that's tied to a germline mutation.
Dr. \And for our listeners, if you haven't heard some of the podcasts that I've done with Dr. Holly uh Peterson, who's talked about caring for patients who have BRECA 1 and BRCA2 mutations as well as well as other genetic mutations, that's kind of a good one to go back to, to listen to, because this is pretty deep stuff. What are some of the limitations or cons of uh uh the ct DNA test?
SPEAKER_01So there are there are of course limitations. Uh not everyone's going to be eligible. So if you're someone who has been disease-free for a long time and your tumor is not banked anywhere, you don't have any of the original tumor, this is not something that's going to be available for you if you're doing a tumor-informed approach, which is really the approach that is really shown the most clinical value. Um so that's that's one limitation for sure. And the other is, of course, that sensity sensitivity and specificity of any diagnostic is always a question. Is a positive or a negative, is it always a true positive or true negative? And that's an always always a question. Now, there's going to be variation across like what's available out there, so you really want to pay attention to that or make sure that's something that's being discussed with whoever your your oncologist is when you when you get a result back.
Dr. \And we have people listening from around the world to our podcast, and you know, they might be at big medical centers with research facilities or small areas, regional, rural, or somewhere in between. Is this really personalized genetic uh treatment for cancer primarily just at the bigger centers?
Early Detection Hype And Risks
SPEAKER_01So, yes. I would say that major academic medical centers are the types of places that are doing the cutting edge precision oncology. It's not to say that it's not found in community settings where actually a lot of oncology care occurs. I think the overwhelming majority of cancer care occurs in that in that setting. And so, yeah, that's not necessarily the most cutting edge. It's hard to keep up with all the changes. I mean, year over year, the practice change, real practice changes are occurring. And if you're not the expert in a specific cancer and you're you're an oncologist who treats many different types of of solid cancers, you may not know what the best approach is for that cancer and may not be doing the most up-to-date offering, or you may not even be your your location may not be equipped. Now, there's all these, of course, send out labs and and other corpor uh corporations that that offer these these testing, uh, these tests, so that there's of course solutions to this, but you're right to point out that some of the the most cutting-edge stuff is available at these major centers.
Dr. \And certainly obviously also enrolling in clinical trials, which people sometimes have rare cancer or young people or very high-risk people, or people that have metastatic disease and don't have other therapies offered to them they want to pursue.
SPEAKER_01Yes, yeah.
Dr. \Any comments about ovarian cancer? We were briefly looking at this OVA-1 blood test, you know, with ovarian cysts to see if it was going to be high risk, like as a tumor marker in the blood, and you know, only one study really showed that. Because a lot of women have to undergo removal of the ovari if it looks like it's cancer, but we don't know, and we don't really have any good screening tests for ovarian cancer.
SPEAKER_01So ovarian cancer, gynecologic cancers are eligible for CT DNA MRD testing, as well as the typical comprehensive genomic uh profiling that's available. So you can all these technologies can be applied to those. And typically those DNA-based diagnostics and assays are going to be going to offer greater sensitivity and specificity than any protein biomarker that that you could come across.
Dr. \But that's assuming you're already diagnosed with the cancer. Sure, yeah. I deal with and am faced with are people that they don't know yet if they have cancer.
SPEAKER_01Sure, sure.
Dr. \That's before that.
Prostate, Breast, And Balancing Overtreatment
SPEAKER_01Yeah, so that's really the the the early detection field. So again, these same technologies can be applied for that. We don't necessarily have great evidence to know whether those are going to be reliable for detecting early stage disease. I would say if you're someone who has late stage disease and it's ambiguous whether it for some reason to diagnose this late stage disease, then the multi-cancer early detection approaches will probably find it with high confidence. But if it's an early stage disease, yeah, I'm not sure we have a great answer for that yet. And hopefully those issues around sensitivity and specificity of the early detection assays can be resolved. And so that's just an active area that that is being worked on right now.
Dr. \Prostate cancer is another common cancer that's kind of vexing in terms of it's pretty easy to diagnose and overdiagnose just with a screening PSA blood test. And whether that disease actually progresses or not, because the surgery is such and the treatments and radiation can, you know, affect someone pretty significantly. So what are what are the advances? Is there any of the CT DNA testing for prostate?
Practicalities, Preparation, And Cautions
SPEAKER_01So you you could I I don't necessarily know exactly what the the latest is in assessing whether prostate cancer is at high risk for you know going metastatic or not. You know, there's there's a lot of different approaches, like we mentioned before, there is that oncotype DX test that's available. There's just doing the comprehensive genomic profiling may tell you if it's more likely to be aggressive or not, because there are some prognostic markers just in the genetic changes in the in the cancer that can be found. P10, a gene that I worked on in in my graduate studies, is an important somatic gene to prostate cancer, for example, as well as the androgen receptor. There are changes that can occur to the androgen receptor and in prostate cancer. So those those can be uh informative. The exact, like how how informative is it? You know, do you want to make exact what decisions you should make based on the information? I I don't exactly know what the latest is there, um, but I'm sure there's there's active work going on and it's improving all the time. There's a lot of different there's there's also approaches that try to pull information from all, like we're getting information from the the tumor DNA, but we're also getting information from blood work, we're getting information from imaging, we're getting information from histology. There's many different ways that we're getting information about the cancer, and there's ways that are they're trying to integrate all that information to then give you a personalized score for what your risk of progression is or not. It's a it's an approach, it's sometimes called like a nomogram approach, when you can like draw a line between all your numbers and then it lines up to a percentile of individualized risk for whatever the question you're asking. And so that's that's an approach that I think has been pursued in prostate cancer as well. So there's there's a lot of different options.
Dr. \Also in breast cancer, because of course a lot of breast cancer survivors after they're done their treatment, many of them want to pursue hormone therapy, and if they've had hormone receptor positive cancer, or even if it's negative cancer, there's a lot of different implications. So we try to mathematically map that out as much as possible. Um I would think if somebody had a negative CT DNA test, they would probably feel more comfortable about you know pursuing therapies that they might not be able to pursue undergoing active cancer treatments.
SPEAKER_01Yeah, yeah. The challenge in prostate is the real question is whether to ressect the cancer or not to ressect the cancer. So the question is a little different where a lot of the time, and when we're talking about MRD testing, is that the cancer has been resected, and the question is is you know, to what extent is there residual disease? How is there residual disease at all, and what do we do from there? So it's it's a little bit different. It's like whether or not to operate at all. And so it's really just trying to you have to find the right set of biomarkers. I don't think we have a perfect answer yet. Although there is some information you can gather, and it's the question is how much of a gambler are you, or how much what is your risk tolerance?
Dr. \Exactly.
SPEAKER_01Is the question.
Substack, Research Sharing, And Closing
Dr. \And it is very individualized. But my concern is over-diagnosing and over-treating cancers. I mean, certainly we know we don't want to under-diagnose those treat those cancers that we can cure and that we understand their biology. But breast and prostate, especially in older persons, also thyroid can be uh thyroid cancer can be over over-diagnosed, but generally ablating the thyroid and giving thyroid replacement isn't as devastating as like taking out the prostate or taking out the breast and preventing hormone therapy. But renal cancer, kidney cancer, is another cancer that can be over-diagnosed. And I'm surprised that some people, since if you have two kidneys, you would think if one had a a lesion on it, you would just take the tumor out, but that's not always the case these days. So it all really does have to be individualized and the whole field is just rapidly expanding. Is there anything that a patient has to do to prepare for this test if they're uh offered it and they can get the tumor signature?
SPEAKER_01Nope, as long as you have that tissue from uh the original original cancer and uh are open to blood uh doing a blood test, which hopefully it's very minimally invasive. So uh that's that's all there that needs to be. So that's what the beauty of the test in in part is it's just as simple as getting a blood test.
Dr. \A simple a blood draw.
SPEAKER_01After the original tumor.
Dr. \I was talking to your uh cousin, my nephew Keaton, yesterday, and he needed to get a blood test. He's like, Ann Hawley, I pass out when I have a blood draw. So for some people it is a bigger deal. But in the grand spectrum of what we do medically, yes, it's generally not that big a deal, which is I think why some people are pursuing, and I don't believe it's covered at all by insurance, but this cash payment of just having even they have no symptoms at all, but they just go in and have their blood drawn to see if they have any kind of marks or do you have comments about that? Well, that raises to me.
SPEAKER_01Yeah, that raises some of the issues that you mentioned before where you can run into false positives and then you have the psychological burden of thinking you have cancer when in fact you don't actually have cancer. And then you could actually have some sort of like low-grade cancer that was actually detected, and and so it's kind of a true positive, but it wasn't gonna be clinically relevant to you at all.
Dr. \Exactly.
SPEAKER_01And so you run into that situation, then you go down various treatment paths, and you're treating the cancer, and you're going through all this in in a way that you didn't need to, it wasn't going to change your life, it wasn't gonna change the length of your life or the quality of life, and you made your quality of life potentially worse because you're enduring the side effects of the treatment and the stress of the treatment and so on. So those are all those questions. So I don't think you want to rush into tests that aren't medically indicated, and so you want to be careful that you're getting a test that you are the right candidate for. Yes. And so, you know, in in the field of genetic diagnostics, we're we're always trying to make sure that that the right people are being tested and that the test is is designed in the way to give very clear diagnoses. It's a challenge because you know the genome is is complicated and there's other many other complications, but I think that everyone's working to try to make that the case.
Dr. \Well, a fascinating, evolving field. And before we wrap up our interview, um, I was hoping that you could share with our listeners a little bit about your Substack and also your X feed. Your X feed is so scientific and so deep and sometimes boring.
SPEAKER_01I guess so. I don't, I mean, I mostly use uh Twitter slash X just to share the latest uh science articles that I find interesting. I don't know if many people will find, you know, that's that's really like the latest, the latest stuff. So it can be uh probably for those who are not used to used to the field, I don't think anyone's gonna find anything of value there. But on Substack, I uh I write at stetson.substack.com and I I write about many topics in science and and literature. I think one of my recent pieces was on uh the question of how do we know that a gene is related to a certain disease condition? What do clinical geneticists, medical geneticists do? How do they figure out that there is a relationship and what is the process for figuring that out? I tried to describe that in accessible language and so on. And then, you know, I do a lot of different book reviews. I reviewed a book recently on the the origins of human language. That's a storied debate in the field of evolutionary biology.
Dr. \I never knew there was so much debate about that.
SPEAKER_01Oh, yeah, it's a huge debate. Yeah. Such a debate, it was it was banned several times by several scientific societies because it was such a sidetracking, all-consuming debate. Read a lot about many different topics there, and so you can find me at stetson.substack.com. It also goes by the name Holodoxa.
Dr. \Very interesting. Well, we'll have to have you back again as this field evolves. I want to thank all of you so much for joining us. If you enjoyed this, please give us a five star rating, share it, and remember be strong, be helping, and be in charge.
