Transcription:
Improved Genetic Testing for Pancreatic Cancer Patients

Melanie Cole, MS (Host): Research demonstrates the importance of genetic testing for all pancreatic cancer patients. This includes patients who were previously tested because there are new, more advanced tests available. We're here to address the new guidelines and why your patients need this test. Welcome to the University of Maryland Medical System, Physician Podcast Series. As an academic medical system, we bring innovation, discovery and research to the care we provide, all while educating the state's current and future physicians and healthcare professionals.

This podcast is sponsored by the University of Maryland Cancer Network. I'm Melanie Cole. And joining me is Katie Bisordi. She's an Instructor in the Department of Pediatrics in the Division of Genetics at the University of Maryland School of Medicine. And Rachel Gore. She's a Genetic Counselor for MSC working with the NIH.

Ladies, I'm so glad to have you join us today. So Katie, I'd like to start with you, please tell us what role inherited trait plays in developing pancreatic cancer and why, and when should a patient get genetic testing for pancreatic cancer?

Katharine Bisordi, MS, MGC, CGC (Guest): Sure. Thank you so much for having us here. We really appreciate the opportunity to talk about this. So, in general, you know, we, and like we always talk with most of our patients, you know, most of the cancer we see is sporadic. For specifically for pancreatic cancer, we believe about five to 10% of pancreatic cancer cases are hereditary.

And even maybe more so when we're selecting those who have a family history of pancreatic cancer as well. As for the why, and when should a patient get genetic testing for pancreatic cancer, there's really two main situations where an individual should consider that. And that is if someone A, has a personal history of exocrine pancreatic cancer or adenocarcinoma. Or if they have a family history of exocrine pancreatic cancer in a close relative, but they themselves are unaffected. So, as for the why and when, if someone has a personal history of pancreatic cancer, it would be best if we could do it kind of right after the diagnosis as part of the whole diagnostic workup.

Because if there is a pathogenic variant identified on testing, this could do a few things for us and for the patient and their treating team. It could help guide potential treatments and targeted therapies, which we will come back to and discuss in more detail in a little bit. It could provide an explanation as to why the pancreatic cancer developed, and this can really be psycho-socially and emotionally important to a patient to know that it was something genetic and not in their control. It wasn't something that they did and help remove any potential self-blame. It can identify other potential cancer risks and screening suggestions for the patient. And it can provide more accurate risk information for family members. And this is something a lot of our patients often want to do. They want to provide more information to their children and siblings to be aware and to be knowledgeable and prepare. And so on the other side, if someone is personally unaffected, but has a family history of pancreatic cancer in a close relative, testing can really be done at any point in time. You know, anytime the family history is known, the goal of the testing for these individuals is to see if they have an increased genetic risk or predisposition to develop pancreatic cancer.

And if then they should consider pancreatic cancer screening. It is important to note here that although genetic testing can technically be done in an unaffected individual, it is much, much more informative to do tessting in a person who has the pancreatic cancer. So, if an unaffected person gets testing and has a negative genetic test, meaning they, no pathogenic variants are identified in any of the genes tested, this does not explain or negate the positive family history. So that person would still be at an elevated risk based on their family history. And that's what we call an uninformative negative. And of course we know that this is not always possible for the more informative person or relative to be tested because they may have passed away or declined testing or whatever other reason. But we always go over these testing limitations in our genetic counseling sessions.

Host: Well, thank you for that. So Rachel, for other providers, what does the research show about the importance of genetic testing for this condition?

Rachel Gore, ScM, CGC (Guest): Yeah, that's a great question. And I think jumping off what Katie said, I'll kind of break this up into two pieces. So the first comes into that scenario where somebody has recently been diagnosed and we're really trying to incorporate genetic testing results into their treatment planning. And so, in recent years there have become available some more targeted therapies that are specifically indicated for people who have a pathogenic variant in the BRCA1 or BRCA2 gene, either a somatic mutation in the tumor itself or a germline variant.

And in particular thinking about PARP inhibitors, which have been used for some time, for breat and ovarian cancer, they are now approved for treatment of pancreatic cancer in the presence of a pathogenic variant in the BRCA1 or BRCA2 genes. And even in some cases in a pathogenic variant in another gene involved in the mismatch repair pathway. So early data has been very promising for these treatments. You know, especially I think for a lot of patients in this situation, they may have tried other things. They may or may not have a cancer that can be resectable surgically. And so having another option for the treating clinician can be very useful.

Eligibility for these medications depends on a number of different factors. So, you know, we of course defer to the treating team regardless of genetic testing results. But having this information quickly, in a timely manner could open up some of these additional options that would not otherwise be available. So that's one very important piece of this. Then when we go to the second scenario that Katie was describing for individuals who carry a pathogenic variant, but do not yet have a history, really the big takeaway there is the availability for screening. If we know that a person is at an elevated risk due to the variant and the family history; we can then now offer pancreatic cancer screening on a clinical basis, which can lead to early identification of pancreatic cancers, which does lead to down staging and increased survival. And there's actually some pretty good data on this. So in a recent large study, 75 to 90% of pancreatic cancers that were detected early by screening; were able to be surgically removed, which is significantly higher than the resectability rates for diagnoses made after the start of symptoms. And resectable pancreatic cancers, as we know, are associated with significantly higher survival rates than those that can not be treated with surgery. So there is good data that early detection does make a difference when we're screening people that are at a baseline higher risk. So, you know, that's some newer data that, we're excited about and I think reinforces the importance of this.

Host: Well, it certainly does. And that is exciting data as you said, especially for these patients and this diagnoses. So, Katie let's speak about the new guidelines for screening and genetic tests for pancreatic cancer and how have they changed over the years. And while you're telling us that I'd like you to speak about the kinds of genetic tests available, whether we're talking about somatic tumor testing versus germline testing for hereditary risks, speak about all of that for us.

Katie: So, in terms of the guidelines, they've changed a lot over the years and really in just the last couple of years here. So we kind of first started out with, there really wasn't much of a mention in the NCCN, National Comprehensive Cancer Network. And so it wasn't really any mention of pancreatic cancer screening that time. And then a few years ago they added some recommendations that, you know, you can consider testing for pancreatic cancer genes if there's also a family history of breast and ovarian cancer, because we know that genes such as the BRC1 and BRC2, they can increase the risk primarily for breast and ovarian cancer, but there also is a link to pancreatic as well.

And then it became really more of a new understanding that grew that pancreatic cancer on its own can be an indication. And this was really added in the 1.2 2020 guidelines. So, really just recently. And then for screening, NCCN used to say, you know, just consider investigational studies and screening on a research basis. Cause we didn't really have any specific recommendations. And then in the 2020 recommendations that were released, this was the first time it really provided more guidance on when, how, and for whom screening should be offered. So again, in the guideline that we're referring to is the NCCN and specifically it's the clinical practice guidelines in oncology, genetic and familial high risk assessment for breast ovarian and pancreatic cancer.

Actually even the title of the guideline changed. It used to be just breast and ovarian cancer, but in the 2020 update it included pancreatic cancer and the title of the guideline. So that current version that's out is now 1.2022, and this was updated last August. So I'm first going to talk about the genetic testing recommendations and then the screening recommendations.

So, for genetic testing, for hereditary pancreatic cancer genes, the NCCN guidelines say that testing should really be offered to all individuals who have been diagnosed with exocrine pancreatic cancer. And to those who are unaffected, but have a family history of a first degree relative. So, we're talking about a parent, a sibling or a child.

So a first degree relative with exocrine pancreatic cancer. It does note that some individuals with a second degree relative with pancreatic cancer may also meet criteria for testing based on additional family history like of breast, ovarian, or prostate cancers. They do not have a specific stance or recommendation about what kind of testing to do.

So this is kind of getting to the question about germline testing options. But there are multiple testing options that are available and this can include single gene or single syndrome. Like if we're looking just at the BRCA genes or just that the Lynch syndrome genes, although I will say it's, pretty rare.

And, you know, Rachel can add to this as well if she feels differently. But I think it's pretty rare that we will just offer testing for a one gene or one syndrome based on the personal and family history. Unless there's a specific known familial mutation in the family, we tend to go for a multigene panel of some amounts.

So, and that multigene panel can look different. It can be a more pancreatic cancer focused panel. So this is going to really focus on some of the genes that are known to be associated with anywhere from a moderately to significantly increase risk for pancreatic cancer. And that might also include some genes for which there is some preliminary evidence looking into pancreatic cancer, but might not have a particular impact on management.

It's more of a an early link in early evidence. And then there's also a broader pan-cancer panel option. So, this is where it's going to include pancreatic cancer genes, but also going to have genes that increases the risk for other cancers, like breast, colon, gynecological, et cetera. They might not necessarily all be linked to pancreatic cancer, but it's kind of a broader casting, a wider net sort of test.

And so as part of a genetic counseling appointment, we take a detailed family history. We review the benefits and limitations of genetic testing, and we work with the patient to see what kind of testing option really fits them and their family history and the level of information they want and the level of uncertainty that they can deal with. So that was about the genetic testing part.

And then through the piece about pancreatic cancer screening, NCCN does now have some recommendations, as I mentioned before, and they're actually going to differ a little bit depending on the gene and the family history that we're talking about.

So there are certain genes that have a higher risk of pancreatic cancer that we would start screening at an earlier age, like as early as age 30. And then there are other genes that have a more moderate increase in risk. So it's not just having the gene mutation, but you also would need a family history of one or more first or second degree relatives with pancreatic cancer to really consider starting any kind of screening starting at age 50 years.

And all of that can be modified based on family history. So, if there is a diagnosis, we would say start by that age or 10 years earlier than the earliest diagnosis. So it can still be further personalized. The screening that's mentioned it would be annual contrast enhanced MRI, MRCP, or endoscopic ultrasound.

And so the screening intervals would also be considered based on clinical judgment. If we need to have a shorter screening interval or if anything, potentially abnormal or concerning is found on previous screening.

Host: Well, that was a very comprehensive answer, katie, thank you so much. And Rachel, if a patient has had genetic testing in the past, do they need to be tested again?

Rachel: Well, like many questions in medicine, it depends. So, mainly it depends on what kind of testing they had in the past. So if they were tested a few years ago, it's likely that only the BRCA genes were tested. And then we would definitely want to consider additional testing with a multigene panelthat includes the more newly identified pancreatic cancer, susceptibility genes.

If someone has already had a multigene panel, though, you know, we're looking at genes that they were born with. So, we don't expect their results to change over time. So, if somebody had comprehensive testing, we don't recommend testing them again. But if it was only the BRCA genes, then it would be recommended for them to have repeat testing with a larger multigene panel. One of the options that Katie went over.

Host: I'd like to give you each a chance for a final thought. So, Katie starting with you, can you please speak about referral for genetic testing and for other providers how do they counsel their patients when they get the inevitable questions? What to do with the information? What must go along with the testing as far as decisions that are influenced by genetic diagnosis, such as management of newly diagnosed patients, management of survivors and implication for relatives

Katie: Sure. So I you know, I think that one of the other general takeaways that I wanted to mention is that it's important to be asking patients about the family history regardless of what specialty. And so, you know, not just asking about family history of pancreatic cancer, but also thinking about, is there a family history of breast, ovarian, colon, et cetera, because that can really open up a lot of potential suspicion for particular genes.

And then in terms of referring, yes, we typically do ask for, you know, a general order or a referral to the genetic counseling program at BWMC. That way, you know, I know who I can also send notes back and forth to and add them to testing orders as well. But it's a really simple process.

And right now I'm seeing patients by Telemedicine. So, also quite easy and for the patients. So, a lot of people will often ask if I do this genetic testing, what is it going to tell me? I already have the diagnosis of pancreatic cancer. And so some of the things that I would suggest you know, in stressing and encouraging to the patient is that, you know, it could open up some therapeutic options for the patient's current cancer, might also open them up to clinical trials and other studies based on the genetic result.

And then you know, largely for our family members. Cause then the question often is, well, what about my children? What's the risk for them? This would be able to provide more direct and specific risk information for family members. So, really the main things to me are potential treatment options for the individual patient and then more refined information for the family members.

Host: Rachel last word to you. I'd like you to give us any takeaways that you'd like to share with other providers and how the field of cancer genetics and genetic counseling is really evolving into this burgeoning field.

Rachel: Absolutely. I mean, it's grown so much even just in the last five years or so. So, you know, like Katie said, I think it's important to ask your patients about their family history and encourage them to talk to their families, be familiar with the guidelines, they do change quickly. And then, really recognize that genetic counselors are a great resource in your area. We're available to speak with providers we're available to meet with patients and we're specifically trained in the area, not only of staying abreast of all of these evolving changes in the medical area, but also in, you know, communication with patients and helping facilitate decision-making and adaptation to results that can be complicated and upsetting for some people.

And so, you know, this is what we do day in and day out, and we really, you know, enjoy and love partnering with physicians. Don't be afraid to pick up the phone and reach out to your local genetic counselor. That's what we're here for.

Host: Thank you so much, ladies for joining us today and sharing your incredible expertise on the topic of genetic counseling and genetic testing and screening for pancreatic cancer. This episode is sponsored by the University of Maryland Cancer Network led by the University of Maryland, Marlene and Stewart Greenbaum Comprehensive Cancer center.

One of the things. NCI designated comprehensive cancer centers. The UM cancer network provides access to national experts, the latest treatments, leading edge technology and promising clinical trials all close to home. The UM Cancer Network helping you beat cancer once and for all. And to find more shows just like this one, please visit us at umms.org/podcasts.

Thank you so much for listening to the University of Maryland Medical System Physician Podcast Series. We look forward to you joining us again. I'm Melanie Cole.