S2E5 | Your DNA and the Cancer Clues That May Be Hiding There
S2E5 | Your DNA and the Cancer Clues That May Be Hiding There
It’s been nearly 70 years since Cambridge University scientists James D. Watson and Francis H.C. Crick discovered the double-helix structure of DNA. In the decades since, our evolving understanding of the human genome has had a profound impact on treatment advances for diseases like cancer. To commemorate Watson and Crick’s groundbreaking discovery, and the mapping of the full human genome 50 years later, DNA Day was designated as a time of public reflection and education around genetics and genomics. To celebrate the occasion, our host, Pat Basu, MD, MBA, President & CEO of Cancer Treatment Centers of America® (CTCA), and his guest, CTCA® Genetic Counselor Eric Fowler, discuss the role genetic testing and counseling play in the cancer journey.
Eric Fowler, MS, LCGCManager, Genetics & Licensed Certified Genetic Counselor
Pat Basu: Hi, I'm Pat Basu, President and CEO of Cancer Treatment Centers of America, and the host of Focus on Cancer. Many of you may not know, this coming Sunday, April 25th is what's known as DNA Day. A very special day in the world of science and medicine that marks the discovery of DNA by Watson and Crick in the year 1953, and also recognizes that 50 years later and another incredible human achievement, the sequencing of the human genome. And what many of you do know is the powerful role that genetics plays in all of our lives and certainly in cancer care and also in the battle against cancer. And that's really the topic of today's episode, and we have an incredibly special guest. Eric Fowler is a world- renowned genetic counselor, a genetic counselor at Cancer Treatment Centers of America, who is really going to walk us through the powerful role that genetics plays in cancer and in fighting cancer. Eric, welcome to the show.
Eric Fowler: Thank you, Pat. It's great to be here.
Pat Basu: Well, Eric, let's start basic and we'll dive deeper. I know a lot of people probably heard about genetic counseling and certainly in the cancer space, but just at a high level, share with us what does a genetic counselor do.
Eric Fowler: So, genetic counselors review people's personal and family history information to look for the possibility or the chances of there being an inherited risk for a disease or a genetic condition within a family. We basically go over information about genetics and cancer and talk to people about genetic testing.
Pat Basu: Tell me, what got you into genetic counseling? Why did you choose to go down that path? And then specifically, because genetic counselors, I know work at a variety of important areas in medicine, why specifically as it relates to cancer and oncology?
Eric Fowler: Well, when I was 10 years old, my grandmother's sister invited me along to do family tree research with her. And in the course of us researching our family tree together, we got to be really good friends. And so, I always have had a passion for genealogy and even looking within my own family at how certain genetic conditions or possibly genetic conditions may be passed down. And specifically, the reason that I became interested in genetic counseling in the cancer space is because that same great aunt that got me interested in our family history and genealogy actually passed away from cancer. So, it's very personal to me.
Pat Basu: Well, I'm so, so sorry to hear about that she passed away from cancer. I know it is wide. So, many of us do what we do and why you and I have been brought to the battle against cancer, but thank you for all that you do. You mentioned this idea of a family tree and really how important that is for everyone to explore. Nowadays, there are a lot of popular tests such as Ancestry DNA and 23andMe, but what you do is you're a counselor, especially in the realm of testing for cancer risk is significantly different. Can you separate those two? How are they similar? How are they different?
Eric Fowler: Absolutely. The direct to consumer genetic tests where a person does not need a physician's order to obtain a testing kit or send a sample in and receive results, really pertain more to ancestry can help facilitate genealogy research into the family tree and really just provide minimal, if any, information about risks for health. The genetic testing that I coordinate for people is very specifically focused on oncology and inherited risks for cancer. We do a deep delve into the genes that we know of that are linked with inherited risks for cancer and provide the type of information that's very detailed, very focused, and can literally change a person's life in terms of knowing about cancer risk. So, the direct to consumer tests are more general, more basic in terms of the information that are provided. And the genetic testing that I coordinate really looks at that person's genetic makeup to understand if they have an inherited risk for cancer.
Pat Basu: Eric, another area where people might have come across genetic testing, I know sometimes is in the prenatal space. How is what you do similar or different than the role of those who might've encountered prenatal genetics?
Eric Fowler: So, some similarities are in both areas of medicine. We actually do take detailed family history information. A cancer focused family tree is looking more at the cancer histories in a family, ages people were diagnosed with cancer, with types of cancer. And in the prenatal setting, it's more focused on any potential history of genetic conditions within that family. So, there are similarities there. Also, in terms of the type of genetic testing, very similar in terms of what we may be looking for on the level of single genes. But oftentimes in cancer, we're using saliva or blood samples to do genetic testing for that individual. But in prenatal genetics, sometimes samples of amniotic fluid are taken or other samples are taken to evaluate the DNA for the baby. And so, there's some similarities there, but a lot of differences in terms of the type of information you may obtain from a genetic test result.
Pat Basu: And before we get too much deeper into, certainly the impact of genetics on cancer care, just the word genetics itself, I think can sometimes mean a lot of different things to a lot of people. What exactly do we mean? How do you explain genetics and genes to your patients?
Eric Fowler: So, I usually start out with the big picture and talk about how our bodies are composed of billions of cells, and inside each cell we have the genetic information or the DNA. This is like a blueprint for everything, from what a person looks like, every trait they have, how their bodies work, even how their cells interact. And we inherit our DNA from each parent, half from mother and half from father. And right now, scientists estimate that people have about 20,000 different genes that make up the human genetic code. And so, we're talking about detailed information going from the big picture, down to the small. I also mention how sometimes genes have mutations in them. These are genetic changes that affect the function of the gene. And most mutations are not inherited, but rather acquired, especially when we're talking about cancer. But the type of genetic testing that I do and what I look for are the inherited mutations that can be passed from parent to child and increase the lifetime risks for certain cancers.
Pat Basu: And Eric, I'm sure you get this a lot from your patients. It's easy to mix up these two terms because they sound very similar to each other. But on a previous episode, we talked a lot about the role of genomics and genomic testing in cancer care and cancer research in contrast to genetics. How do you clarify that for your patients and our listeners?
Eric Fowler: Basically, genetic testing is done to look for an inherited risk for cancer. We do look for these inherited mutations that can be passed from generation to generation, and the testing is done on healthy cells, blood or saliva, typically. Genomic testing is done to look for potentially different treatment options for people who've had a cancer diagnosis, looking for acquired mutations within the tumor cells. And this testing is done on the actual cancer cells, rather than the healthy cells we use for genetic testing.
Pat Basu: So, we've laid a great foundation. Let's get much more specifically into the incredibly important role that genetics plays in cancer care, and you mentioned inherited cancer risk. So, there are what we refer to as inherited cancer syndromes, which is really when you look at a family tree, it is an increased hereditary risk that is of a certain cancer type that is passing on through that patient's gene pool. And these are often characterized by their specific name of a gene or gene mutation. BRCA is probably one of the more high profile, more well- known genes that gets talked about in the breast cancer arena. Give us an example of an inherited cancer syndrome, how it works from a genetic standpoint, maybe almost just take us through one of those examples end to end.
Eric Fowler: Absolutely. So, there is a genetic condition that's even more common than having a BRCA1 or 2 mutation or the hereditary breast ovarian cancer syndrome. And this condition is called Lynch syndrome. And it's named after Dr. Henry Lynch, who first suspected and then was proven right, that there may be an inherited risk involving certain types of cancers in families. And when a person has Lynch syndrome, they have higher risks for colorectal cancer, stomach cancer, endometrial cancer, ovarian cancer, and to a lesser extent, other cancers as well. So, knowing that, that condition is there can really be very important because it allows that person and family members who may also have testing truly understand what their risks are to be proactive about risk and take steps to manage their care that are empowered.
Pat Basu: Absolutely. And that's a great example of Lynch syndrome. Can you clarify, you said something earlier in your comments that you really focus on the inherited cancer risk, but obviously, there are non inherited risk factors developing cancer. Let's talk about the difference between inherited genetic risk versus acquired. I'm sure you talked about that with your patients.
Eric Fowler: Yes. So, most changes in genes or what we call mutations are acquired during a person's lifetime. We all go through life, we have exposures to certain things in the environment that may cause DNA damage. So, these are acquired mutations and common across probably all cancers that occur. But it's really only about 10 to 15% of people who have a cancer diagnosis actually have an inherited mutation that put them at higher risk for cancer and acted as a susceptibility or a risk to the cancer occurring. And so, we can say, really, that there's that common genetic basis for cancer, but it's only a subset of people with cancer actually have an inherited risk for the diagnosis. And I'd also like to say that having an inherited risk for cancer does not mean that a cancer will happen. It means that the risk is higher than average, what those risks are depend on the gene or the syndrome. So, definitely, not everybody who's inherited a risk or a mutation that increases their chances for cancer will develop a cancer.
Pat Basu: So, this is probably one of the most important aspects of the show and certainly, how this pertains to genetic testing and cancer. So, I think, just to be clear, patient, so five to 10% of genetic mutations are hereditary, meaning that the others are acquired. So, let's call it 90 to 95% are acquired, which basically means that even if you do not have, let's say, an inherited mutation that gets detected on a genetic screening, it does not mean by any stretch that you are clear or going to be cancer free. And so, thus the important role of prevention and screening and diagnostic testing, which we've talked about on this show previously. Alternatively, if you have an inherited genetic mutation with a higher predisposition for developing cancer, it doesn't necessarily mean that you will develop cancer for sure. So, given that some might say," Well, Eric, why get genetic testing in the first place then, if neither pathway is really a guarantee of safety or a guarantee that you're going to have it? Why get the testing done in the first place?"
Eric Fowler: That's a great question. And definitely, patients do ask that. One of the main points is that knowing you have a higher risk for cancer can allow for various specific screening options to be undertaken and covered by insurance companies. These tests, for example, with Lynch syndrome, colonoscopies. Starting colonoscopies by age 20 to 30 years old and repeating them every one to two years is the recommendation. You could find a precancerous polyp and remove it, thereby preventing that colon cancer from ever starting. So, it can change in terms of screening. We may offer risk reducing options that can reduce the possibilities of a future cancer happening. Again, with Lynch syndrome, an example would be the higher risk of uterine or endometrial cancer for women with the condition where with the medical guidelines, we discuss women with Lynch syndrome would consider a risk reducing surgery, a hysterectomy to reduce their risks. So, it's really knowing what the risk is to be able to either find cancers earlier, if they were to happen, or reduce their risks of occurring. And also, in some cases to really reinforce the importance of our behaviors, our lifestyle choices, there are certain genes that increase the risk for melanoma. And if somebody knows they have a mutation, one of those genes, hopefully it would reinforce their behavior to do what we all know we should do, which is to wear a sunscreen if we're out and we're in the sun for long periods of time, also to wear protective clothing and even possibly to choose a career path that didn't keep them outside doing their work. So, really, there's a lot of aspects to how knowing there's an inherited risk can change medical management.
Pat Basu: Risk and statistics can be a hard thing to fully individualize. But oftentimes, I use metaphors such as, if you're driving a car and you know that you have a bad wheel, or maybe you inherited a bad wheel, that is not a guarantee of a car accident down the road, but you're going to be more cautious about it. You're going to pay attention to it. If there's something you can do to, of course, correct that, you will. And so much of what we're talking about is about risk understanding, risk mitigation and or risk reduction. And then, as you said before, altering behaviors, altering future therapies that can keep patients as safe and away from this horrible disease as possible. Furthermore, Eric, obviously as you know, genetic testing can help inform the treatment decisions, once a patient does develop cancer if they're going to. So, tell us more about the role that inherited genetic risks can play, not only in the diagnosis of cancer, but how that can alter the way that we would actually treat a cancer that's been diagnosed.
Eric Fowler: It was very exciting within the last several years when there was research done that showed if a person had a certain genetic mutation that was inherited, for example, BRCA1 and 2 mutations, that could be helpful to the oncologist in guiding specific treatment options and recommendations for that person. So, for example, people who have BRCA1 or 2 mutations with certain types of breast cancer, ovarian, prostate, or pancreatic cancer, maybe offer different sorts of targeted therapies that they wouldn't otherwise be offered. And that's really a conversation between the oncologist and that individual, in the context of their genetic test results. But it's really exciting times because I can remember many years when there were no such options like that available and genetic testing and results were not ever referred to or used in that capacity.
Pat Basu: And Eric, we talked, again, and you did a great job explaining the difference between genetic testing and genomic testing. Can you maybe double- click into that concept where, let's just say a patient has had a positive finding, a inherited genetic risk of a certain cancer with a cancer type. How might genomic testing of the tumor itself play in or out of that scenario? Can you give us maybe an example?
Eric Fowler: Sure. So, with the finding of an inherited risk for cancer on genetic testing, you may or may not find that same marker in a genomic test. Probably most of the time you would, but there are times because the tumor DNA can be very different from what's present in other cells in the body. So, knowing that there is an inherited risk, you may not have that information from the genomic test itself. Genomic testing is, again, looking for changes in the DNA and tumor cells. There are times when genetic mutations that are inherited may show up in the tumor. Now, we can't differentiate what's inherited or not and times when they don't. So, sometimes it's good to double check and you may have some discrepancy between genetic and genomic test results.
Pat Basu: Very helpful. And as we're having this discussion, I'm sure some in our audience are saying," I'm convinced that I'd like to get tested. I need to get tested." It's not exactly that simple. It's not yes or no. Talk to us about the decision to get genetic testing.
Eric Fowler: Genetic testing is definitely a very personal decision. And basically, at this point in time, there's not population- wide genetic testing to screen for inherited risks for cancer, although, that has been discussed within the genetics community. The reason that there is not population- wide screening for inherited risks for cancer, there's several. One of which is there are far more people who do not have an inherited risk for cancer in the population at large than those who do. So, you would do many, many, many tests, potentially to find a person with an inherited risk. Another reason is cost. Who would pay for the genetic testing? And there definitely are criteria, medical criteria that guide physicians and clinicians and genetic counselors on offering genetic testing to people, but also insurance criteria. And without those criteria being met by an insurance company's perspective, genetic testing may not be covered. And another thing to consider is that when we do genetic testing, we don't always get informative test results. There's times where genetic tests may find something that's uncertain or unclear in a gene, and so genetic testing does have the potential to raise questions. So, these are all things that have to be considered when someone embarks on the genetic counseling or genetic testing journey.
Pat Basu: So, Eric, who then should get considered for genetic testing?
Eric Fowler: There are guidelines that have been published and they've been refined over the years, and they're constantly changing as we learn more. But in general, if a person has been diagnosed with cancer at an earlier than average age, say under 50, or if they have a relative with a diagnosis at an earlier age, that might be a consideration. If you have multiple people in the same family, who've had the same type of cancer or even different cancers that can track back to the same inherited risk. If there's a generation to generation pattern of cancer in a family where you may see a grandparent, their child, the grandchild with cancers coming down that line of the family, that is suspicious, that there could be an inherited risk. And also, some aspects of ancestry can play a part. And for example, if someone has Eastern European or Ashkenazi Jewish heritage, that does increase the odds in the setting of a breast, ovarian, pancreatic, or prostate cancer, that there may be an inherited risk. So, we take all these things into account, but then something more new in terms of being an indication for a genetics consult are the genomic test results. When we do genomic testing, we're looking at the DNA in the cancer cells to help guide treatment. However, if somebody has inherited a risk for cancer, if they've inherited a mutation, it's there at conception and likely, in every cell in their body. So, often, if somebody does have an inherited risk for cancer, we'll see some suggestion of that on the genomic test results, where we find a difference in a gene that is a gene that we know is linked with inherited risks for cancer. Just by virtue of the genomic test results, we can't tell if what we're seeing is inherited or not. And so, to better understand that, a referral to a genetic counselor and then genetic testing will help to differentiate between differences in genes on the genomic test in the tumor that are acquired or are inherited. And one example of this is I worked with a man once who had lung cancer, and he on his genomic test had an alteration in the BRCA gene. One of the BRCA genes, I believe it was BRCA2. And he had no significant family history of any BRCA related cancers, no breast, no ovarian, no pancreatic cancer, but just that presence of that marker in the tumor DNA prompted the referral by the oncologist. We did genetic testing and we did find that, that BRCA alteration in the tumor was present in healthy cells as well, and therefore, it was an inherited risk, which was of immense help to his family members, several of whom went on to have genetic testing and tested positive. And we never would have evaluated that person or family or offered genetic testing otherwise.
Pat Basu: Well, that's a very pointed example on a really good segue and then actually a thought or a question maybe I had for you is, aside from the ability of a patient to reduce their cancer risk, there are other reasons why a patient might want to pursue genetic testing for personal reasons. What would you say are the most common reasons you hear from patients?
Eric Fowler: I think the most common reason that I hear is a concern for children. A person saying," I'm doing this test, not only for myself, but also to help inform my children of any potential risks that they could have inherited from me." Sometimes people are also looking for answers as to why they had a cancer diagnosed. And while genetic testing and a positive result where we find a mutation may not be the only answer, it does give us a window into that person having a higher baseline risk or risk to start with that they could have had a cancer in the first place. So, sometimes people are looking for answers. And also, as we've been talking about for that proactive aspect, that planning aspect, that ability to address a personalized risk based on a positive genetic test result. So, I think these are probably the main reasons and motivations people have to proceed with a genetic test, looking for an inherited risk for cancer.
Pat Basu: So, Eric, what are some things that people should be mindful of or cognizant of when seeking genetic testing?
Eric Fowler: Pat, I think one of the most important things is to, as much as a person can, think ahead. We each know ourselves better than anybody else in the world. To think about," What if I did test positive for a mutation and inherited risk for cancer? How would knowing that impact me on a day- to- day basis? Is it something that I would be able to put out of my mind until screenings or interventions come up or would it be something that would be present and thought about more often?" Also, family relationships, because genetic testing can impact an entire family in finding an inherited risk. For example, if two sisters tested positive for a BRCA mutation, but the third sister didn't in that family, how would the sisters who tested positive feel about their sister who tested negative? And vice versa, that person who didn't inherit the mutation, would she have survivor guilt? Would she feel guilty that even though it was out of her control that she inherited that risk herself? So, that's definitely one of the important things to consider. Also, insurance coverage and costs. Will the testing be covered? What would be the potential cost if it wasn't? Genetic counselors are specially trained to look at that information and help act as a guide to people through the genetic testing process. And also to talk about privacy of the information. How will this information be kept in my medical record, who will have access to it? These are very important things to think about. And it's part of the genetic counseling process that we talk to people about these things and work with them so that they can think through these processes and these possibilities.
Pat Basu: Your example of the sisters and the BRCA mutation are so many other powerful examples of the consequences of getting positive results. It brings up what will seem like a simple question, but I think a really important one is, what are the various results that you can get from a genetic test?
Eric Fowler: The positive result that we've been focusing on is, as we mentioned, we do find an inherited risk for cancer. There is a mutation that can be passed from parent to child. Close family members of that person like children and siblings would each have a 50% or one in two possibility that they also inherited that risk. The second result is a negative result where we do the test and we find no differences of any kind in any of the genes that were evaluated. And in many ways, this is hopeful because it does significantly reduce the odds of an inherited risk for that person and in that family. But I think that there are genes yet to be discovered, and it's likely that genetic testing techniques will improve in the future. So, we always encourage people to check in periodically, who've had genetic testing without any findings. The third result is neither a positive or a negative. It's where we do genetic testing and we may find a difference or what we call a variant in a gene. And whether that variant has any impact on how the gene works or consequently risks for cancer, is uncertain or unknown. So, that's an inconclusive test result. And so, the genetic counseling does involve reviewing all of these possibilities with people so they're prepared for whatever the outcome may be. And the last two results, the negative and the inconclusive are lumped together into the uninformative test result category. We didn't find any proof of an inherited risk. There were no markers found, but yet, at the same time, you still have to pay attention to family and personal histories in guiding care.
Pat Basu: So, a relatively finite set of options there. Of course, the inconclusive is one of those results that across the board can sometimes be a little bit frustrating, I would say, for folks, even though, as we discussed earlier, a positive is not a guarantee of developing cancer, a negative is not a guarantee of not developing cancer. So, I think that should be taken in context. But what happens next after an inconclusive test, more tests are performed or surveillance, or what do you recommend to patients in that case?
Eric Fowler: After an inconclusive test result, we refer back to that person's personal and family histories to help guide future cancer screening. And so, that's an important part of the process. In terms of additional genetic testing after an inconclusive, typically not. What happens is the genetic testing laboratory, and these are independent laboratories, reference laboratories, not affiliated with any hospital or clinic. The genetic testing laboratory will keep watching that particular variant as more families are tested, to see if they find that variant in other people who are tested through the laboratory. They will watch research studies that are published, to see if there's any new data on that particular variant to allow them to form an opinion about whether that variant is meaningful. And also, some labs have internal ways that they can evaluate a variant that may provide even additional information with further studies on the sample that's already been received. That may not happen this year or next, but it could happen in the future. So, if an inconclusive test result is reclassified, whether as an inherited risk or a benign change in the gene that doesn't matter, the ordering physician's office or genetic counselor is notified of that update and then we reach out to that person. And most of the time, when a variance that's unclear or what we call a variant of unknown significance is figured out or reclassified, it turns into a benign change in the gene that does not have an impact on risk.
Pat Basu: So, Eric, after that tremendous explanation of the testing process on the foundation of everything you already covered, it brings me to probably one of the most important points is I find the role of genic counselor to be one of the most important in not only just healthcare, but very specifically in cancer care. I think, just your explanations, your very coherent walkthrough of the process and the results has illustrated that. But let's talk about the role of the genetic counselor in the cancer care continuum. Can you share for our audience the progression of how a patient interacts with you or a genetic counselor in cancer care, in the role of how you help them interpret the results, so on so forth?
Eric Fowler: Sure. So, typically a person would be referred by a physician or an advanced practitioner, or a physician's assistant or nurse practitioner for the genetics consult. The initial session or what we sometimes call the pre- test genetic counseling session is one where the genetic counselor gets a sense of that person's personal and family history, the likelihood there could be an inherited risk. And we really review the option of genetic testing. Genetic counselors by training are non- directive, which means we never recommend a genetic test to somebody, but rather we work with that person to help them explore their motivations to have, or not to have a genetic test. And we act as support in that way. After the initial genetics consult, if that person is going to have a genetic test, the genetic counselor will help coordinate that testing. There's the sample collection, which typically is blood or saliva. There are consent forms for genetic testing, which are that person's written permission to have the genetic testing, which cover the contents of the genetics consult. And then, once genetic test results are back, they are then relate to that person for a post counseling session, whether a telephone conversation, an in- person consult, a tele- health visit, where the results are reviewed in detail on how they impact not only that person, but their family members too.
Pat Basu: And in order to go through just the important technical aspects of genetic testing, let alone, as you mentioned before, the deeply personal, potentially psychological impacts that these can have. What type of education and training should people be familiar with when it comes to speaking to their genetic counselor?
Eric Fowler: Genetic counselors typically come from an undergraduate background of biology, chemistry, from time psychology. And then we go on to get master's degrees in medical genetics, or genetic counseling. So, it really is a unique combination of the science aspect of genetics and the counseling aspects to be able to provide emotional support to people when they may be learning difficult information or going through the genetic testing process. Genetic counselors are certified by the American Board of Genetic Counseling and about two thirds of states in the US have licensure available for genetic counseling. So, genetic counselors, depending on where they live, always are reaching towards being board certified or board eligible and state by state attaining their licensure for genetic counseling.
Pat Basu: Well, Eric, this has just been such a great walkthrough into an important, and sometimes maybe under covered or underappreciated aspect of a real foundational, very important aspect of the battle against cancer. Tremendous strides have already been made in our ability to look for inherited cancer risk, our ability to, as we mentioned, alter the treatment based on those findings. But paint for us your vision of the future. What might we expect? How will the field evolve in say five or 10 years? What will we be able to do that we can't do today?
Eric Fowler: I think that there will be new genes identified that are linked with inherited risks for cancer, genes that we do not know about today, cannot test today. So, that's an ongoing, evolving process. It takes the identification of a candidate gene to then proving there's cause and effect with that gene in cancer. But I do think we're going to find more genes of that type. I think the genetic testing technologies will be improving, where they'll be even more accurate than they are today. And they are very, very accurate today. And I think there's going to be more availability of targeted therapies and treatments based on finding somebody who does have an inherited risk for cancer than we have available today, which are just for certain genes and future certain cancer types. So, in the future, I think we have a lot of hope looking forward that genetics will be an even better tool than it is today, to help people and families through the cancer journey.
Pat Basu: Wow. What a tremendous vision and just what a privilege to have you on the show, Eric. This has been terrific and I know incredibly educational for so many of listeners. I really appreciate everything that you do. I know, firsthand, how much patients appreciate what you do, and we're grateful for your time. And thank you. Keep up the great work. It's great to see you.
Eric Fowler: Thank you. Great to be here.