Genetic Tests and Cancer

Transcript of Episode 9: Genetic Tests and Cancer
The Thing About Cancer podcast, Cancer Council NSW

[Series intro]
[woman] The very essence of all cancers is a change in the way that cells divide.
[music]
[man] I remember sitting in there thinking, you know, it’s not happening, it’s not real, it can’t be real.
[woman 2] It’s something that we don’t talk about
[woman 3] This feeling of being overwhelmed − it will get better once you have a plan and you know what to expect and what’s going to happen.
[woman 4] It’s not going to be like this all the time
[various voices] The Thing About Cancer: A podcast from Cancer Council NSW.
Information and insights for people affected by cancer.

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Julie McCrossin: Hello, I’m Julie McCrossin and today the thing about cancer is that these days more and more it’s talked about as a “genetic disease”. What exactly does that mean for people with cancer? How do you find out if cancer runs in your family, and how can genetic tests help you and your doctors work out the best treatment path?

Dr Hilda High: Cancer genetics can provide a lot of information. Particularly if you think it will change what you do, or how you do it, then you should try and get that information early.

Julie: We’re talking to Dr. Hilda High. Hilda is a genetic oncologist and works in private practice as the head of Sydney Cancer Genetics. Just to be clear, this podcast contains general information only, so we recommend you talk to appropriate professionals about your individual situation. You can also call Cancer Council 13 11 20 if you have any questions. Welcome to the podcast, Hilda. Tell me what does a genetic oncologist actually do?

Hilda: A genetic oncologist is a cancer doctor, an oncologist, who is specialised into hereditary cancers.

Julie: And when you say hereditary cancer, what do you mean?

Hilda: Some people have a mistake in a gene, we call it a mutation, that’s being passed down in that family and that particular mistake is increasing their risk. So, in their case, there is a hereditary component. Most cancer is not hereditary.

Julie: So, hereditary means that the cancer runs in the family, it’s inherited. What proportion of cancers are inherited?

Hilda: It depends on the cancer. The more common the cancer, the lower the percentage. So, with breast cancer, it might be only 3 per cent of all breast cancer; bowel cancer, it’s about 3 per cent; but when we look at ovarian cancer, of a particular kind, you may find that it’s 20 per cent or more, and in some very rare cancers, such as medullary thyroid cancer, it may be 50 per cent or more.

Julie: People are often surprised if they’re diagnosed with cancer − I know I was − because there was no family history, but in fact most cancers aren’t inherited. So, why do those cancers happen?

Hilda: Most cancer occurs because of mistakes that build up over time in our cells. If a cell collects enough of those mistakes, then it will grow when it shouldn’t, and not die when it should, and stop following the rules. And that’s what cancer is. But those mistakes have usually only happened in that cell, usually many years after you’ve had your kids − they weren’t inherited, and they’re not passed on.

Julie: Okay, so what I’m understanding is that all cancer is caused by mistakes in genes. Sometimes it’s because you’ve inherited a mistake, so that’s hereditary cancer, but more often it’s just a mistake that’s developed in your body over time and we’ll talk more about that later in the podcast. But let’s start off with genetic testing for hereditary cancers. If you’ve just got a cancer diagnosis what questions should you ask your medical team about genetic testing?

Hilda: It depends a bit on the type of cancer and how old you are. I think that talking about genetics is always important and the basis of that is making a family history: Who had a cancer? What age? What type? Once you’ve done that, then you can either be reassured that these cancers have occurred in the 70s and 80s and it really is great genes living a long healthy life. For other families, the pattern may emerge that there really may be something going on, or it might be that you have a triple negative breast cancer, and therefore, there is a chance that there is a mistake in the gene that caused this cancer to occur.

Julie: So, basically, if you’ve just had a diagnosis, it’s worth asking family on both sides of your mum and dad, do we have any cancer in the family?

Hilda: That’s true, and that’s very true as well because people seem to think that you inherit breast cancer genes from Mum and prostate cancer genes from Dad, but we get half our genes from Mum and half from Dad. So, these things can come from Dad’s side of the family as well.

Julie: So, if I could put it this way, is it ever appropriate to have a genetic test to see if you may get cancer?

Hilda: That’s true in that if your mother passed away from an ovarian cancer when she was in her 40s, there’s a 20 per cent chance that may have been caused by a mistake in a gene, one that you have a 50/50 chance of inheriting. So, in that situation you’re having a test to see whether you carry a mutation that increases your risk. But a genetic test cannot tell you if you will get cancer, or the age, or the type.
It is just going to tell you about your “risk”.

Julie: And if a member of my family is diagnosed, when would it be appropriate for me to get a genetic test just in case it can give me information that will help me stay healthy?

Hilda: It’s always better to test the person with the cancer. There’s no point in testing other family members until you’ve worked out what’s going on. Once we know of a mutation in a family, then it’s very important to offer that test to other adult blood relatives. We call that “cascade testing”. The mutation is being passed down in those families and you want to know: am I at risk, or not?

Julie: Can a genetic test ever show definitively that you will not get cancer?

Hilda: No. And the classic example here is, if we have a known mutation in a family that increases cancer risk, BRCA1 for example, the people who do not carry the BRCA1 mutation, the women in that family, are still at population-based risk for breast cancer. It might only be 10 or 15 per cent over the whole of their life, they may just need mammograms every two years, but they are still people, they still have cells dividing, they are still at risk of cancer.

Julie: Is this something you could talk to your GP about, or your medical oncologist, or do you need a genetic oncologist like yourself?

Hilda: I think the first discussion can be with a GP or a medical oncologist just to sort of say, no, these are great genes, everybody’s had a cancer at an older age, there’s not that much cancer. But at the time you’re trying to work out which test and what is it going to mean, there is a lot of expertise required to interpret that appropriately.

Julie: Let’s get down to the nitty-gritty of it though. What does the test involve?

Hilda: The test itself is simple. It’s just two tubes of blood collected 10 minutes apart. What we want is access to the DNA that made you, from when you were one cell big. The easiest way of getting it is through our white cells and they’re easily collected through a blood test or even a saliva test. The DNA is extracted in the lab and then we just look at the section that we’re interested in: the specific gene or genes associated with the cancers in the family.

Julie: I’ve heard that some hospitals have a “familial cancer centre”. What exactly is that?

Hilda: It’s just the term used for the public clinics where the focus is on hereditary cancers, usually staffed by a genetic oncologist or a clinical geneticist and genetic counsellors.

Julie: And under what circumstances would you be referred to such a place?

Hilda: You can refer yourself, or your GP or your specialist will refer you. The idea is if you’ve got three cancers in two generations, one under 50, that’s worth at least thinking about and discussing with your GP. Some cancers we know have a very high chance of a mutation. Those are the ones where you may be referred specifically to look into that particular cancer or that particular gene.

Julie: And what are the most common cancers that will get you referred to a familial cancer centre?

Hilda: Ovarian cancer. Breast cancer diagnosed at a young age or of a particular type called triple negative. Bowel cancer with a specific staining test showing a possible mistake in a gene. Things like medullary thyroid cancer, which is a rare form of what may be a not-so-common cancer. It’s really about young-onset, rare type, and more cancer in the family than we would expect.

Julie: If you want to find out more about these clinics, you can go to our podcast page at cancercouncil.com.au/podcasts and click through to this episode. We’ve put a link to a list of those familial cancer centres, and also a link to the website of Dr Hilda High’s Sydney Cancer Genetics. Tell me, Hilda, are these familial cancer centres found everywhere? What if you live in regional Australia?

Hilda: Most familial cancer clinics are based in metropolitan centres and that can be very difficult for somebody who’s having treatment and lives in a rural and regional area. To get to some of these centres we do “telehealth”, which is simply doing a consult via a video conference, either via Skype or something like that. I conduct telehealth to rural and regional Australia, so Northern Territory, Tassie, anywhere that’s outside a metropolitan centre, and we do that to a patient’s GP. It means that they can attend with their family, and also their GP can sit in, and learn about that specific cancer or the genes involved.

Julie: You work in the private sector − are there differences in experience for public and private patients when it comes to discussing genetics?

Hilda: The main difference is in the private I can only bill for the face-to-face time, so I do everything with you. In the public, people may be salaried and as a result a lot of it goes on behind the scenes. You might fill out forms, send them back in, somebody might contact you and you may end up simply with a letter saying: you’re not eligible, this doesn’t look like a high-risk family. A lot of work may have been done but you may not be aware of that.

Julie: When someone’s referred to you as a genetic oncologist, what do you do with the patient?

Hilda: My consults take an hour, and when you arrive we sit down, we go through your personal history, review the cancer pathology if you’ve had a cancer, go through the family history and draw up a pedigree. So, we can see at a glance who’s had cancer: what age, what type. Then I go through roundabout a 20-minute discussion of what cancer actually is, how it is caused, and why it may or may not be hereditary in you or your family. We then discuss what genetic testing is, what it involves, whether it’s even appropriate for you and your family, and we talk about what we’re going to do with the result. Then we can talk about which specific test or tests we should do, and if you’re not the best person to test in the family, we have forms that we use to try and send that information to family members to get more information about what’s gone on in the family and perhaps to do testing elsewhere. And at the end, we go through how to keep you and your family healthy and safe regardless of whether we do a genetic test.

Julie: There are pros and cons of getting tested, aren’t there? Can you just give me an overview of what might be some of the arguments for and against having that genetic test done?

Hilda: So, I think one thing people don’t think about is that when we do a genetic test we might find a funny change. We don’t always know what those changes mean. And many people choosing to have a genetic test are doing it because they want reassurance that they’re not at risk. Those changes, we call them variants, can actually increase anxiety. Secondly, I think it’s very important not to misunderstand the result of a genetic test. Not finding a mutation, does not suddenly make your family history disappear.

Julie: So, if I’m understanding you correctly, if part of your goal in inquiring about a genetic test is to have some certainty and to remove ambiguity, it may not achieve that because it’s still a question of professional judgement and a range of possibilities?

Hilda: That’s true. The only time that we really have that level of certainty is when we’ve found the cause for the cancers in the family and shown that you have not inherited that, and that’s not the most common scenario.

Julie: Can you give me an example where that does happen though, just so we understand that?

Hilda: Absolutely. So, let’s say there’s a family history of bowel cancer. We do a staining test and it suggests that it could be the MSH2 gene. The person with the cancer has a genetic test and a spelling mistake is found in that gene that means that gene isn’t going to work. What we then do, is we test that person’s brothers and sisters, parents, and adult children. And what we’re trying to find out is, have you inherited that mistake, are you at risk? And it’s 50/50. At the point that you have inherited it, we can use screening, colonoscopies and other things to reduce your risk.

Julie: So, in other words, watch them more carefully.

Hilda: That’s right, and then for those family members that have not inherited that mutation, their risk of the cancers associated with that goes back to being pretty much average.

Julie: So, in a nutshell there are some cases in which the tests can clear away anxiety or let you and your doctors know that you need to be more watchful and do regular monitoring tests to catch any issues early. But in other cases, it won’t clear the ambiguity. Look, a lot of us have heard about Angelina Jolie having both breasts removed after having genetic testing. Can you explain why that may have been done?

Hilda: Angelina inherited, like we all do, a copy of the BRCA1 gene from her mum and the copy of the BRCA1 gene from her dad. So, you get half of your genes from your mum, they come over in the egg, and half from your dad in the sperm. In her case, she inherited a copy that had a mutation. Because that means that she’s got an increased risk of cancer − and in her case that was somewhere between a 40 and 80 per cent lifetime risk of breast cancer and a 20 to 60 per cent lifetime risk of ovarian cancer − Angelina then chose to reduce her risk. She may have done that through screening, but she chose to do that through bilateral mastectomies and removing her tubes and ovaries.

Julie: And bilateral mastectomy means both her breasts were taken off?

Hilda: That’s right, she had the breast tissue removed. By doing that, her risk of cancer is actually less than the [average] Australian woman’s, significantly less actually. So, what a hereditary cancer syndrome tells us, is about risk. It cannot tell you if you will get cancer or the age or the type. It can simply say you’re at high risk and then you can do something about reducing that risk.

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Julie: You’re listening to The Thing About Cancer, a podcast from Cancer Council NSW. I’m Julie McCrossin and I’m talking to Dr Hilda High, a genetic oncologist from Sydney Cancer Genetics about the role of genetic testing in cancer treatment.

If you have any questions about this topic, or just want to talk to someone about your concerns, you can call Cancer Council 13 11 20. For links to more information or any of the services we mention − or to listen to more podcasts − visit cancercouncil.com.au/podcasts. In a moment, Hilda is going to explain more about genes and DNA, how genetic tests can sometimes help doctors work out the best treatment path, and ways you might be able to access genetic testing.

Julie: Let’s go back to basics. This word “genetic”, what does that mean?

Hilda: So, genetic relates to genes. We have 22,000 genes and they each have a role. We don’t necessarily always know what that role is.

Julie: What is a gene?

Hilda: A gene, in simple terms is a recipe. Most genes are a recipe for a protein and then that protein has a function. Our genes are written in a code. That’s the DNA code, made out of the letters A, T, C and G.

Julie: Right. So, if the gene is a recipe, the DNA is the code in which the recipe is written. Where exactly do you find the DNA?

Hilda: So, nearly every cell in our body has a nucleus, and it’s inside the nucleus that the DNA is. If you think of a gene as a, a recipe book, they sit on “shelves” − the chromosomes. So, it’s like books on a library shelf. The cell uses whichever book it needs to when it needs to make something, usually it’s a protein. One example of our genes is the BRCA1 gene, it makes a “spell-checker”. So, if you want to spell-check then you turn on that gene and you go ahead with your spell-checking.

Julie: When you say spell-checking, what’s it checking?

Hilda: So, when a cell makes a copy of itself – and you’d know that your skin’s growing, your hair is growing – when a cell turns over, it has to make an exact copy of itself, and that means copying out all of your DNA. That’s nine billion letters of code, and if you were to type it out, it might take you two years. I don’t know about your typing, but if it was me I’d make some mistakes, and that’s what happens in our cells. Those mistakes, though, can happen anywhere in that nine billion letters of code, and when those mistakes aren’t fixed, they’ll be passed on the next time a copy is made.

Julie: And is that series of mistakes the beginning of cancer?

Hilda: That’s exactly right. Now if the mistake was in a gene that told you how to grow fingers and toes when you were a baby, it won’t matter. But if it’s in a gene that tells that cell when to grow, you’ll now have a cell that grows when it shouldn’t. That could be a polyp in your bowel, or a lump or bump, it’s not a cancer. But if that same cell dividing and growing, just in the breast or in the bowel, continues to build up more mistakes, which it will, and those mistakes land on key genes, you might end up with a mistake in a gene that tells that cell when to die. Later on, a cancer protection gene, or a spell-checker gene, or even a how-to-be-a-breast-cell gene, if enough of those mistakes build up in any one cell, that cell is going to grow when it shouldn’t, not die when it should, and stop following the rules, and that’s cancer.

Julie: You’re explaining to me why some cells will overproduce and become cancer and it’s to do with rare genetic events − is that what you’d say?

Hilda: So, the mistakes are common, but what happens is for them to land on one of these very important genes is rare. So, if I was to take a little bit of tissue from a 70- or 80-year-old from all different parts of their body, I’d find most of those cells will have some mistakes. But they won’t be in the kind of gene that’s really important − a gene telling that cell when to grow, when to die, and how to behave.

Julie: So, this is why cancer is sometimes called a genetic disease, even though in most cases, it isn’t inherited?

Hilda: You’re absolutely right. All cancer is genetic, because it’s all caused by mistakes in genes. But those mistakes have just built up gradually and so as those mistakes build up, the cell may continue to function quite well, or it may end up with a mistake that’s really important. If that mistake builds up in the breast, then you’ll end up with a breast cancer. But that’s why most cancer occurs at an older age: breast cancer in the 50s, 60s and 70s, bowel cancer, again in the 50s, 60s and 70s.

Julie: Can genetic testing also be used after you’ve been diagnosed with cancer to work out what sort of treatment would be best?

Hilda: It’s got to do with the type of cancer. Sometimes it’s very important to ask: what went wrong? What went wrong specifically in this cancer, because that can help us target our treatments and may change whether or not chemotherapy is even recommended, radiation given, and so on.

Julie: I’ve heard that with some cancers your doctor might talk to you about giving a “genomic assay”. Is a genomic assay a genetic test?

Hilda: Strictly speaking, when we use the term genetic test, we mean a germline genetic test − in other words, what came over in the egg and the sperm, what did you inherit? When we’re doing a genomic assay, we’re asking: What mistakes built up in this cancer? Where are its weaknesses? What can we target? What can we exploit?

Julie: So, a genomic assay is a test that can find something to “target” in a cancer. Is that related to targeted therapy?

Hilda: So, targeted therapy is simply finding a very specific change in a cancer that we can match with a treatment. For example, if you have a mistake in the BRCA1 gene, you may be able to use something called a PARP inhibitor. We know the PARP inhibitor won’t work if the BRCA genes are working fine.

Julie: And is that a medication?

Hilda: It’s a medication used to treat ovarian cancer and possibly later prostate and breast cancer.

Julie: So, under what circumstances would you be advised to have a genetic test in the hope of getting a targeted therapy?

Hilda: Targeted therapies tend to be expensive and so they’re not usually used as the first-line treatment. The targeted therapies don’t work unless the target is present. So, there’s no point in spending money, taxpayers’ or your own, on a treatment if it’s not going to work.

Julie: Look, we’re actually also doing a podcast on new therapies that talks more about targeted therapy, so if you want to know more, you can look for that on our podcast page, at cancercouncil.com.au/podcasts. And look, another thing that keeps coming up in the news and other places is “whole genome sequencing”. Can you explain what that is?

Hilda: So, the “sequencing” means going through and spell-checking, looking for the order of the letters in that code. “Whole genome” means looking at all of our genes: 22,000 of them. So, whole genome sequencing creates a large amount of data but not always a lot of usable information. So, most whole genome sequencing is done in research. We don’t know the names of all those genes and we certainly don’t know how they all work. So, it really is very much a research tool.

Julie: But online you see advertising for genome sequencing, even whole genome sequencing. You can even be suggested to send it away overseas. What is your view on that?

Hilda: First of all, read the fine print. Most often these things will say “analysis not included”. In other words, that’s like saying: I will spell-check your Encyclopaedia Britannica, but I’m not going to tell you where the mistakes were or what they mean. Secondly, the fine print’s also important in how the DNA is handled. There are some overseas companies who, perhaps like Amazon, make their money from the data rather than from the genetic testing, and they do tell you that they will sell your DNA to third parties including parties outside the US. That may not be an issue, but you would want to know. In Australia, we store the DNA. That means that we can go back and test it at a later time, but it remains your DNA and it’s not tested or sent elsewhere without your permission.

Julie: So, if someone’s had a cancer diagnosis and they want genetic testing, what are their options and how much does it cost?

Hilda: Genetic testing can be expensive, although the costs have come down considerably. We use models, “risk predictors”, to work out what is the likelihood in this person, with this cancer, in this family history, that there is a mutation in a particular gene. Generally, if that likelihood is 10 per cent, then a publicly funded test may be offered. If there’s a 9 per cent chance, then you may not be offered a test, but you could pay for your own testing. If there’s a 1 in 1000 or 1 in 10,000 chance you’re better off not having the test. So, sometimes it’s important to talk about the family history with the GP, or ask the GP or your specialist to use eviQ, the Cancer Institute’s guidelines − that will help them determine, is this a high-risk situation or not?

Julie: We’ve indicated that this is a developing area: our knowledge of genetic testing, whether it may be of value or not to the individual, and sometimes this is covered by Medicare and public funding and sometimes it’s not. As a patient or family member, what criteria should I use to decide whether I should go for privately funded testing?

Hilda: In general, most people don’t need a genetic test of the kind that looks for an inherited mutation. But some people do. And assessing that with your GP and coming and talking to a genetic oncologist can be really important. I think even just knowing that privately funded testing and private clinics exist. I think it’s also important to know that just because somebody is selling something, doesn’t mean you have to buy it. If you’re going to pay for a test, you need to know: how are they going to do it, what are the results going to mean, and who’s going to explain them to me? Because if you spend a lot of money on a test and you simply get a great big report, you will then want somebody to explain it to you, and if you go back to the public system, you may be waiting 12 or 18 months for that appointment. And for some people enrolling in research may be just as cost effective and equally useful for that person. So, if you’re interested in, say, the Innovate Cancer Trial which looks at causes of ovarian cancer, you can enrol in that trial and then the testing is done for free.

Julie: Can you explain what a clinical trial is and how that might arise for an individual?

Hilda: A clinical trial is simply set up to answer a question: does this therapy work or does this work better than something else? So those trials are usually very specific and there’ll be what are called “enrolment criteria”.

Julie: So, is it fair to say that generally people may have the mainstream standardised evidence-based care but sometimes perhaps if they have more advanced cancer, they’ll be approached by their clinical team, to see if they’re interested in a clinical trial?

Hilda: Absolutely. Clinical trials are often used after standard therapy, or in rare or unusual cancers.

Julie: If you want to learn more about clinical trials you can read Cancer Council’s booklet “Understanding Clinical Trials and Research”. You’ll find a link to that on our podcast page at cancercouncil.com.au/podcasts and just click through to this episode. Is it fair to say this is a developing area of medicine and research and it’s literally changing almost month by month?

Hilda: That’s actually true. It’s something I write on my letters to say, this is an area of ongoing research and rapid change. And I think, for that reason, people who have had an assessment 5 or 10 years ago, may well want to come back even if just briefly to ask: Has anything changed? Am I eligible for a test now, when I wasn’t before? Because we do change our guidelines and we do change what we can and can’t test for.

Julie: Just finally, can you put on your sort of “future glasses” and tell us where is genetic testing heading? What’s coming down the road?

Hilda: As the costs have continued to fall, I think more people are realising that private testing and self-funded testing is an option. I think there will be more of that and I think we will actually identify more people who are at risk and therefore give them options to reduce that risk. I also think we will do more testing of tumours matching that with a blood test, looking for treatments, and also trying to understand why cancer occurs and how to prevent it. I also think we’ll realise that just because targeted therapies exist doesn’t necessarily make them better. Old effective treatments that may be inexpensive are still effective. I think there will be a focus on “whole person” methods of reducing cancer risk. We know from population studies that we can reduce the risk of cancer by about one-third through things like a healthy diet, exercise, those sorts of very general but very effective ways of reducing cancer.

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Julie: Well that’s it for this episode of The Thing About Cancer. Thank you very much to Dr Hilda High for sharing her knowledge and insights.

If you’re looking for more information, you can ring the Cancer Council 13 11 20 Information and Support Service from anywhere in Australia, or go to cancercouncil.com.au/podcasts. If you have any feedback on this podcast, we’d love to hear from you. So, leave us a review on iTunes or on our website. If you’d like to subscribe to the show you can do it in Apple Podcasts or your favourite podcasting app.

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Julie: If you found this episode useful, you might be interested to know that we’re doing a podcast on weighing up the options before having cancer treatment. We talked to Professor Lyndall Trevena about being involved in treatment decisions, getting a second opinion, and asking questions.

Lyndal: I think a lot of people facing cancer treatment decisions, obviously it’s very difficult. One of the things that often weighs on people’s minds, at that time and later on, is – did I make the right decision? And I think you know you can be satisfied that you have if you’ve done your best to get all the information, consult all the right people, weigh it all up, and that’s the best you can do at that time. So, do that, do that when you have the opportunity, and then don’t look back.

Julie: Look for that episode, Making Treatment Decisions, on our website at cancercouncil.com.au/podcasts.

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The stories and experiences contained in this podcast represent the views and opinions of the speakers. They do not necessarily represent the views and opinions of Cancer Council NSW. This podcast contains general information only and Cancer Council NSW recommends you obtain independent advice specific to your circumstances from appropriate professionals. I’m Julie McCrossin and you’ve been listening to The Thing About Cancer, a podcast from Cancer Council NSW, produced by Jenni Bruce and Miles Martignoni.

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