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Understanding Inherited Cancer Syndromes: Insights and Innovations · Talking FACS

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  Welcome to Talking FACS, and thank you for tuning in to Cancer Conversations
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  on Talking FACS, a podcast collaboration between the University of Kentucky
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  Markey Cancer Center and the UK Martin-Gatton College of Agriculture,
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  Food and Environments Cooperative Extension Service.
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  We will share with you the latest developments in cancer prevention,
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  diagnosis, treatment and research from the experts at Markey Cancer Center,
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  Kentucky's only National Cancer Institute designated Comprehensive Cancer Center.
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  Talking FACS is hosted by the UK Family and Consumer Sciences Extension Program.
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  Our educators share research knowledge with individuals, families,
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  and communities to improve quality of life.
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  Hello, and welcome to Cancer Conversations on Talking FACS.
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  This is your host, Dr. Jennifer Hunter, Assistant Extension Director for Family
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  Consumer Sciences at the University of Kentucky. Today, I'm pleased to be joined by Dr.
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  John D'Orazio, Chief Division of Hematology, Oncology, Department of Pediatrics,
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  University of Kentucky Markey Cancer Center. Welcome, Dr. D'Orazio.
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  Hi, Dr. Hunter. It's great to be here. We appreciate you joining us today.
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  And the topic that you're going to share with us is we're going to focus on
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  inherited cancer syndromes.
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  And really we're going to try and answer the question of if I've had someone
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  in my family or I have a close relative that has a certain type of cancer,
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  how do I know if I have that gene or how would I even begin to explore if I
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  have that gene or maybe even calm some fears about having a genetic-related cancer?
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  But I would like to start off with just the term inherited cancer syndrome.
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  Could you define that for us? Explain it to us a little bit.
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  Yeah, so I work in the world of pediatric oncology, that means children and
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  young people when they get cancer would come to our clinic and we would treat them.
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  And almost as a rule, when a child or young person presents with cancer or comes
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  in with cancer diagnosis, families want to know why. Why my kid? Why my brother?
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  Why my sister? You know, my nephew, so forth.
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  Turns out that about one in every 10 young people that come in with cancer may
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  have inherited, will have had inherited a gene variation or mutation that makes
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  them at increased risk of cancer, okay?
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  One in 10. That means nine in 10 do not. It just is something called sporadic cancer.
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  It was just random bad luck that they came down with the cancer.
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  About 10%, more or less, of our patients might have a gene or do have a gene
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  that explains why they may have gotten their cancer.
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  That's what I mean by inherited cancer syndrome, that they have a.
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  Inherited propensity to cancer, and then that's why they got cancer.
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  As a parent, I can only imagine having a child that may have a cancer diagnosis
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  of that searching for answers, as you just said, or the worry about your other children, et cetera.
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  Are there certain types of pediatric cancers that are more likely to be inherited than others?
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  Yeah. So it's not uniform across the board. The most common type of childhood
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  cancer is acute lymphoblastic leukemia, ALL.
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  And this has been a great success story through a lot of research over the last
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  several decades and teaming up.
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  Most of the time when ALL happens, it's not usually in the context of an inherited cancer syndrome.
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  Sarcomas are solid tumors that happen, so tumors that make a ball and cause
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  problems because they hurt where they start or they're causing problems where they are in the body.
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  About one in five children and young people with sarcomas might have an inherited cancer.
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  So the incidents, so they're overrepresented in the inherited cancer world.
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  But there are dozens now of distinct inherited cancer syndromes,
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  each of them caused by a separate gene that has been mutated or has a change
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  in the DNA sequence from normal.
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  And those lead to specific kinds of cancers at specific points of a child's life, patient's life.
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  So is there testing that has done for inherited cancer syndrome?
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  So here's the thing about that. So we know that about 10% of kids and young
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  adults, and actually grown people too, the numbers hold true even for adults with cancer.
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  It's about one in 10 will have an inherited cancer thing.
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  Very famous like BRCA1 and breast cancer and ovarian cancer, right?
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  People have heard of that because of actors like Angelina Jolie.
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  You know, made her story public and so forth.
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  There are professionals, cancer genetic counselors, and we have them in the
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  marquee and they're awesome and they're just fantastic and able to take a patient's
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  story, the patient's family story,
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  figure out like, is there too much cancer in that family?
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  Is everybody getting a similar kind of tumor?
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  These are all clinical clues that tell us that there might be an inherited cancer syndrome at play.
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  So too much cancers in the family, same kind of tumors in the family,
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  a person who gets an adult kind of tumor way too young, like a 12-year-old with
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  colorectal cancer, for example,
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  and things like that, clues like that, or getting two kinds of tumors over the
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  course of a lifetime. That's unusual, right?
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  And so you could go to a genetic counselor at Markey, a cancer genetic counselor,
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  and they say, oh, it seems like you might be at risk of this syndrome,
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  and they'll test you for that one gene.
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  We've got a different approach in pediatrics, and I'm very sort of proud of
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  this because it's a pretty unique thing that we can do here.
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  And it's called agnostic testing.
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  And we call our program, it's a clinical study, it's called Project Inherited Cancer Risk.
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  And basically, it allows us to offer next-gen whole exome sequencing,
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  so pretty fancy DNA sequencing to look for these genes and their changes in
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  any of our patients who've presented with pediatric cancer, okay? So it is.
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  Kind of expensive. We were able to negotiate the price down a little bit to
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  make it more affordable.
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  We were successful in telling very generous people in the community about this
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  who then funded us to be able to do the sequencing.
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  And then we applied for a grant from the state and got funding to do the sequencing.
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  And so now we're able to offer this to our patients. We have had this clinical
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  study open since August of 2021,
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  and we've sequenced about 220-some children and young adults,
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  adolescents and young adults.
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  And we're finding about an 8% hit rate of these gene changes.
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  And what happens when we find one of these is that it can make a very big difference
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  into how we're going to treat our patient, how we're going to look at their,
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  if they've got cancer at the time, how we're going to treat their cancer,
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  because sometimes having one of these gene changes means we have to do things
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  a little differently with our therapies, because some of the therapies are going
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  to be way too toxic in the setting of that gene change.
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  But it also has a lot more other implications.
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  So, it implies, so more than two-thirds of children with cancer will survive
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  their first cancer, their cancer.
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  And that's one of the optimistic reasons why I went into this field,
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  because you can make a difference and most of my patients are going to do well, right?
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  And so that makes me feel good. But if they've got this gene,
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  the gene wasn't only in their tumor cells, it's in their body.
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  They were born with it. So they could be at risk of more cancers as they grow and develop and age.
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  And so we have to enroll them in very personalized surveillance plans to catch things early.
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  And maybe even, I mentioned Angelina Jolie, you know, she had the BRCA1 mutation,
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  she chose to get mastectomies to avoid the breast cancer risk.
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  So maybe even to prevent cancers with approaches like that.
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  That was going to be my follow-up question was about the surveillance that once
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  you knew that the child had the propensity to have a genetic or inherited type
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  of cancer, what was the next steps?
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  Yeah. So the other thing I'm very proud of in our division is that we actually
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  have a clinic to take care of these young people who have these syndromes.
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  I identified this in like 2019 to,
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  2020, that we were getting referrals from the Markey Cancer Center,
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  who's got this very strong cancer genetics program, who are testing patients
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  because they smell that there could be one of these cancer syndromes at play.
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  And then they find it in somebody, and then there's cascade testing of the family
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  members if they want to do that. And that includes children.
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  And so, So what do you do with a child that's got a gene mutation that might
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  increase their risk of colorectal cancer early in adulthood or even in their teenage years?
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  It's too much to ask a pediatrician to keep track of all these things.
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  Really, there are literally….
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  50 or more of these kind of distinct syndromes. And all of them have specific
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  tumors that are, you know, at increased risk at different times of life.
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  It's just too much to keep track of.
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  So we opened up a clinic called the Cancer Predisposition Clinic in our Dance
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  Blue, you know, pediatric oncology home.
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  And Dr. Amanda Harrington is a wonderful oncologist who has an interest in this.
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  And she is the medical director of that.
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  She and I see these patients and we keep track of it. We have a nurse navigator.
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  Some of these syndromes are lifelong.
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  There's one called Lee Fraumini that puts people at increased cancer risk for
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  their whole life and their guidelines that we can follow to say,
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  oh, they need an annual MRI. They need colonoscopy starting at a certain time of their certain age.
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  They need this. They need that. Mold checks for melanoma. And we keep track
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  of that with a nurse navigator called Heather Straub, who's fantastic.
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  And we engage this community and we provide a medical home, whether or not they've had a cancer, right?
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  So if a family member came in with one of these syndromes and we test other
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  children in the family or young people, they may have it.
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  And then the whole point is to try and catch cancers early because they're going
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  to be much more treatable when they're caught early.
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  Amazing service available through Markey. And that's one of the things that
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  I've really enjoyed about doing this podcast is learning so much about the vast array of services.
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  And you've mentioned several just as we've been chatting here that are available
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  through the Markey Cancer Center.
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  For individual that may have a child with a pediatric cancer diagnosis on the
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  east end of the state or the western end of the state that might not be being treated in Lexington,
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  but they have a concern about potentially having a genetic mutation or a genetic
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  form of cancer, what would be their steps to take.
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  All right. So this is the other exciting thing. So this year,
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  actually today, came through my email, I think maybe the final piece of the
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  puzzle so that we can expand this into a statewide effort for Kentucky.
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  So we started Project Inherited Cancer Risk. It's a little over three years
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  old at the University of Kentucky.
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  We were successful in expanding our grant coverage to incorporate the University
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  of Louisville Norton Children's Hospital.
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  Our two centers, Kentucky Children's Hospital at UK and Norton Children's Hospital
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  at UL are the only two places in the state really where children with cancer should be taken care of.
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  So a person who is in the state of Kentucky who gets treated at one of those
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  two centers will now be eligible for this inherited cancer syndrome clinical study.
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  If they don't get treated at either of those two centers, say they go to somewhere
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  else, West Virginia, Cincinnati, Vanderbilt, wherever, I don't know what options are in those places.
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  I think, you know, without a study such as ours, you're left with going to a
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  cancer genetics counselor and seeing if there's enough clinical clues for them
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  to say, we should test you for this gene.
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  But I know from reading, you know, the literature that we miss about half of
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  all patients who haven't inherited cancer syndrome if we just rely on the clinical clues.
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  So that's why I'm so happy to be able to offer this particular study to the
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  children of Kentucky now. Yeah, that is amazing.
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  Dr. D'Orazio, thank you so much for joining us today and bringing awareness
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  to our listeners regarding inherited cancer syndromes.
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  For our listeners in the show notes, we will have links to the UK Markey Cancer
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  Center to follow up and learn more information. Thank you again.
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  My pleasure. Thanks so much for spotlighting this.
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  Music.