From chemotherapy to immunotherapy and targeted drug delivery, what’s next for breast cancer treatment?
From chemotherapy to immunotherapy and targeted drug delivery, what’s next for breast cancer treatment?
In this episode, Jessica is joined by cancer research expert Associate Professor Pieter Eichhorn, who is co-leading an Australian Government subsidised drug delivery project that aims to change the behaviours of proteins found in breast cancer.
Together, they discuss what conventional treatments exist and where they’re going, Associate Professor Eichhorn’s exciting new drug treatment, and what he believes needs to change to drastically reduce the rates of breast cancer going into the future.
Associate Professor Eichhorn’s research project is supported by the Curtin Health Innovation Research Institute and the National Drug Discovery Centre at the Walter and Eliza Hall Institute.
How breast cancer develops [01:15]
Predicting future rates of breast cancer [04:26]
Progress in conventional treatments [07:56]
What’s unique about the drug delivery project? [13:27]
Associate Professor Eichhorn’s research journey [17:34]
Reducing rates of cancer through tumour sequencing [19:45]
Content note: This episode predominantly covers the experiences of women who are cisgender. Cisgender women are those women whose sense of their gender matches the sex they were assigned at birth and who are the population group at greatest risk of contracting breast cancer.
WEHI: National Drug Discovery Centre announces new projects
National Breast Cancer Foundation website
Breast Cancer Now website
Connect with our guest
Pieter Eichhorn is the Dean of Research Infrastructure at Curtin University, and an Associate Professor at the world-renowned Curtin Health Innovation Research Institute.
He has devoted his career to developing targeted treatments for breast cancer and melanoma patients. Prior to Curtin, he has worked at a variety of prestigious institutes including Harvard Medical School, Massachusetts General Hospital, the Cancer Science Institute of Singapore and the Netherlands Cancer Institute.
Associate Professor Eichhorn’s staff profile
Associate Professor Eichhorn’s LinkedIn profile
Curtin Health Innovation Research Institute website
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Jessica Morrison: 00:00 This is The Future Of, where experts share their vision of the future and how their work is helping shape it for the better.
Jessica Morrison: 00:09 I'm Jessica Morrison. Breast cancer is the most commonly diagnosed cancer in Australia, with 55 Australians diagnosed each day, according to the National Breast Cancer Foundation. In total, 1 in 7 women are currently expected to contract breast cancer in their lifetime. In this episode, I chatted with Associate Professor Pieter Eichhorn, a cancer treatment specialist from the Curtin Health Innovation Research Institute. We discussed what conventional treatments exist and where they’re going, Pieter's exciting new drug treatment, and what he believes needs to change to drastically reduce the rates of breast cancer going into the future.
Jessica Morrison: 00:51 Just as a short note, when Pieter mentions the experiences of women in this episode, he's predominantly referring to women who are cisgender. Cisgender women are those women whose sense of gender matches the sex they were assigned at birth and who are the population group at greatest risk of contracting this disease. If you'd like to find out more about this research, you can visit the links provided in the show notes.
Jessica Morrison: 01:15 All right, Pieter. So to start us off, how does breast cancer develop?
A. Prof Pieter Eichhorn:01:20 Yeah, first of all, thank you for inviting me on this program today. It's been really a true honour to be here. Cancer or breast cancer, like with all cancers, really initiates due the changes in expressions of proteins inside the cell. I think some of the things that we need to recognise is that when clinicians look at tumours or different types of cancers, they look at the organ or the type of tissue that's there. And my work really looks directly inside the individual cells that make up that tumour.
A. Prof Pieter Eichhorn:01:49 So, if you think of a cell as like a refrigerator inside your kitchen, and if you open up your salad drawer, let's say we're some really strange family and inside our salad drawer, that's where we keep our cookbooks. Well, it's those cookbooks that sort of ... When we read those cookbooks, that's what develops all the proteins that make up everything that makes up that fridge.
A. Prof Pieter Eichhorn:02:12 So it makes up all the broccoli that's there, the cheese, the milk. Everything inside that fridge is made up from those cookbooks, including the fridge itself, the coolant, even the plugs that plug into the wall. So if you look at those cookbooks and you look at a certain recipe inside that cookbook; if you have a spelling mistake in one of your recipes, well, maybe that protein that gets read by that spelling mistake, it doesn't really change that much. But if a word's missing, well, then maybe that protein completely changes its form or shape. You can also have multiple different types of mutations. For example, if you had a recipe that says, "Add one teaspoon of sugar", and all of a sudden a mutation says, "Well, now you have to add 111 teaspoons of sugar." Well, that completely changes the recipe. And that happens a lot in all cancers.
A. Prof Pieter Eichhorn:03:04 So all of a sudden, whatever those mutations that occur inside your recipe, that really changes what we see happening inside that fridge and that's really what we see happening inside the individual cells and that really plays a role in overall tissue. But one other thing that happens, besides the mutations that we see in the DNA and that affects protein development, is what's happening outside that fridge, what's happening outside the cell. And one of the things that we see, what really matters, is the micro environment around that individual cell. And a lot of these things are related to hormones that are outside. So for example, oestrogen is a major, major player in breast cancer. So if you imagine your fridge again with your cookbook, it really matters, first of all, is the recipe you're going to make, but also matters how many people are going to come to dinner.
A. Prof Pieter Eichhorn:03:52 So when you're pregnant, you're not cooking for one person, you're cooking for a lot of people because all these hormones are coming in and that's going to make the cell look a little bit different. However, later on at menopause, you're not going to be cooking for 10 people anymore, because the hormone levels decrease a lot. And so you only might be cooking for one or two. So it's the mutations in the DNA, which affect protein production, but it's also your micro environment outside that affects your protein production and it's those changes in those levels of the protein production, which affect breast cancer and the breast cancer proliferation.
Jessica Morrison: 04:26 I've never heard it described like that, but thank you for that description. It was really, really interesting to look at it that way. Into the future, Pieter, can we expect to see the rates of breast cancer increase or decrease?
A. Prof Pieter Eichhorn:04:37 Well, I think there's a couple factors here. One is diagnosis. If we have early diagnosis and better ways to diagnose early stage breast cancer, then of course, because we see an increase in the numbers, we have an increased chance of seeing an increase in the levels of breast cancer going up. But there's a number of other factors that affect breast cancer and one of those things is having earlier periods in younger women. That has been shown to have an increased role in breast cancer and also late stage menopause. So women are having menopause later and therefore that also affects breast cancer progression. There's that greater chance of that oestrogen, which changes the protein levels inside your cell, to then increase the level of proliferation of certain cells in your body. And then that can grow out and grow out.
A. Prof Pieter Eichhorn:05:22 But one of the biggest factors is women are having their first child much later in life. And there's a correlation with having that first child much later in life and breast cancer progression. Conversely, it's actually shown that if you have a child quite early on, there's actually a lower chance of getting breast cancer and it all has to do with these different hormone levels. So if you have a prolonged increase of oestrogen over your entire life, there's an increased chance of getting breast cancer. So why are these younger women that have these children at these really young ages, having a lower-level chance or lower chance of getting breast cancer? And you got to think of it this way. So each cell has these little antennae on top of them and these antennae recognise how much oestrogen is in the system.
A. Prof Pieter Eichhorn:06:09 So if you, at a really young age, you have high levels of oestrogen that are there during your first child. Maybe some of these antennae get a little damaged. So they can't recognise in the future how much oestrogen is there. And so they, say these really, really, really high doses of oestrogen that are coming on at these young ages, well maybe that sort of dulls the system and that's why these women don't have a higher chance of breast cancer later on. So in terms of the incidence of breast cancer, there is an increase in incidence of breast cancer because women are getting menopause later on, they're getting their period earlier on and also the changes in when women are having their first child.
Jessica Morrison: 06:47 Do we know what percentage of people will be affected by cancer in the future?
A. Prof Pieter Eichhorn:06:52 Well, you have to realise with a lot of these cancers, that 70% of us will get cancer in our lives. I think it's just a fact of life that if we live long enough, all of us are going to get cancer. But it's not what it was 30, 40 years ago. If you can cut it away, it's fine. So if you get breast cancer, I mean, 50% of women with breast cancer are completely curable. In some cases it's worse to get diabetes than it is to get breast cancer. But unfortunately some breast cancers are incurable. Right? And so that's what we're really working towards. Testicular cancer is completely curable. Melanoma is completely curable. You cut it away.
A. Prof Pieter Eichhorn:07:32 Unfortunately, when you get melanoma going to different parts of the body, then it becomes very, very difficult to treat. If there's a patient that comes through the clinic and gets a drug and the tumour melts away, they won the lottery ticket. I know it sounds strange, but it does. There's some very, very difficult to treat tumours and the patients are completely curable. Right? And you go, "They just won their lottery ticket."
Jessica Morrison: 07:56 Speaking of treatments, what conventional treatments currently exist, why do we use them, and what progress do you expect to see from these into the future?
A. Prof Pieter Eichhorn:08:06 So there's two really, really main types of treatment for breast cancer. The first one is the type of treatment that damages your DNA. Now that sounds illogical because mutations in your DNA cause cancer. But the reason why we have these mutations in our DNA is because each single cell has repair mechanisms. So if there's a mutation inside your DNA, the cell has these repair mechanisms [that] will come along and fix them. And go, "Oh look, here's something wrong in this DNA, we'll come along and fix it." But it turns out in a lot of cancers these repair mechanisms are actually the ones that are mutated and broken down. So if you have a cancer cell that can no longer repair itself as well as a healthy cell, well, what happens if we really increase the amount of mutations in that cell? So when you give chemotherapy or radiation therapy, the idea is we're going to put as much damage on your cells as possible because the cancer cells can't repair it.
A. Prof Pieter Eichhorn:09:16 And so if you increase the mutations, all of a sudden this goes, "Oh, we just can't survive." But your healthy cells still have that ability to repair all that radiation damage. So the mainstream, since the 50s and 60s, is using high levels of chemotherapy and radiation with the idea to really, really increase the mutation rate in your sick, cancerous cells, because they can't repair it. Your healthy cells will survive and therefore you will survive. The other type of treatment is targeting oestrogen. So because oestrogen is one of the main players in breast cancer, if we stop oestrogen affecting the proliferation potential of these cells, then we can directly target that and decrease the tumour growth. The biggest drug out there is tamoxifen, which targets the ability of oestrogen to increase the proliferation of individual cells. Now, the number of women that get treated with tamoxifen ... It's probably the primary treatment of women. Fifty per cent of women that receive breast cancer are completely curable, and one of the reasons is because of tamoxifen and the targeting of oestrogen in these women.
Jessica Morrison: 10:33 So it's a very effective treatment?
A. Prof Pieter Eichhorn:10:35 Tamoxifen is a very, very effective treatment for those tumours that are dependent on oestrogen.
Jessica Morrison: 10:42 But I'm guessing from that response that not all tumours are respondent to that, are they?
A. Prof Pieter Eichhorn:10:46 So there's other types of breast cancer. Remember I talked about those antennae on top of the cells? Well, there's one that detects something called "oestrogen", and there's another one that detects a different type of hormone. And that antenna is called "HER2". And HER2 is over expressed in about 15% of all women, of all breast cancers, and we have a different type of drug that targets that antenna and that's called "Herceptin" or "trastuzumab". And that revolutionised probably about 25 years ago, the treatment of these women. So basically HER2 induces the proliferation of these cancer cells, and we have the ability to now inhibit that antenna. So we have drugs that target the antenna that detect oestrogen and we have drugs that have the ability to inhibit those hormones that target HER2.
A. Prof Pieter Eichhorn:11:39 But there's another type of breast cancer called "triple-negative breast cancer" that doesn't express any of these antennae. So it doesn't express the oestrogen antenna. It doesn't express the HER2 antenna, and there's another type of hormone: "progesterone". It doesn't detect that one either. So because it doesn't express any of these antennas, there's no real targeted therapy that we can use for these types of tumours. And that's when chemotherapy and radiation therapy really, really come into play for these women with triple-negative breast cancer.
Jessica Morrison: 12:09 It's really interesting to understand that because you sort of, in the mainstream, you hear about breast cancer, but obviously from what you've just said, there's lots of different types and obviously different treatment options.
A. Prof Pieter Eichhorn:12:17 Yeah. So I talked about the different types of treatments for targeting and the oestrogen, but one of the big things that come out recently is talking about immunotherapy, which is a true game changer in the treatment of cancer. So a lot of the cancers have this ability to tell the immune system that, "We're okay, we're fine." In a lot of the cases, normal cells, when they become sick or have a virus inside of them, the immune system will go, "Oh, no, no, there's something wrong with you." And the immune system will come along and just kill it off and take it away and the body stays healthy.
A. Prof Pieter Eichhorn:12:54 Well, cancer cells have that ability as well. The cancer cells have the ability to tell the immune system that, "We're okay, we're fine. We can keep growing. Don't stop us." And a couple years ago, I would say about 10 years ago now, it turns out that we can now reactivate the immune system. We can target those antennae on top of the cells to tell the immune system that we are sick. And so that has been a real game changer and that has really brought along cures for a number of different cancers.
Jessica Morrison: 13:27 So you are leading some really exciting research, Pieter, that could present another treatment option. Can you describe how your research differs from the options we've just discussed and how long it will be until you can take it into the market?
A. Prof Pieter Eichhorn:13:39 Yeah. When I was talking about recipes earlier, and those recipes inside your cookbook, making different types of proteins, there's two types of proteins that get made. And one type of protein's called "oncogenes". And those oncogenes, when they have altered expression, induce the proliferation of cells and there's a type of protein that gets made that's called "tumour suppressors". And those tumour suppressors will look at the whole cell in general and go, "Nah, something's wrong, and we stop", and the whole cell will die. So these tumour suppressors are really, really important for all the checks and balances to make sure that everything's working properly. And a lot of those cases in cancer cells, those tumour suppressors are switched off. There's something wrong with the recipe inside the cookbook that it's just not getting read properly. So we designed a drug that makes sure that we can alter the expression of these tumour suppressors, that makes it really, really high.
A. Prof Pieter Eichhorn:14:40 So in those cancers where these tumour suppressors aren't being read properly and they can't control all the checks and balances that are going on in the cell, the drug that we've designed increases the expression of those tumour suppressors, reactivates them. And now they look at the cell and go, "Oh no, no, things are wrong now. We're going to switch off and we're going to die." Right? So basically when we overexpress or we reactivate these tumour suppressors that are mutated in cancer, we're reactivating those checks and balances that are no longer there in a lot of the cancers.
Jessica Morrison: 15:15 When might we see this on the market?
A. Prof Pieter Eichhorn:15:17 There's a lot of things that you have to realise in drug development. So we made this initial discovery about two, three years ago. We applied to the National Drug Discovery Centre at the Walter and Eliza Hall Institute in Melbourne and we got a grant to look at and [identify] a number of these different chemicals. So when you do that, you have an experiment set up. We then throw 400,000 different chemicals on top of that, with the hope of identifying one or two, which actually work. We don't know what these chemicals are. Well, we know what the chemicals are, but they're not on top of our head. Right? These are just random chemicals that are found in nature. Hopefully with a bit of luck, you find one. So we've identified about, I think, six or seven right now that have the potential to move forward.
A. Prof Pieter Eichhorn:16:10 It's going to take us two, three years to really analyse the specific chemicals that we've identified. Can these chemicals go inside the cell? We don't know that yet. We still have to identify it. Does it actually bind to the protein that we're interested in and can that activate at a great length? Again, we don't know that. So we can then change how the chemical looks to make sure that it's more active, more specific, can enter the cells and doesn't induce toxicity in patients. At that stage you then go into Phase I clinical trials into patients to see if there's any toxicity. It then goes into Phase II and then Phase III.
A. Prof Pieter Eichhorn:16:53 And that whole stage takes about 10 years. From the time you've made your first discovery to the time that it actually is used as a treatment for women takes about 10 years. So it's a long, long period. It just takes that long to make sure that everything's right. Does it work? Is it beneficial to women? So it just takes that very, very long procedure to go through. And it takes millions of millions of dollars. A Phase III clinical trial in breast cancer costs a billion dollars. So the cost of that and what goes forward is huge as well.
Jessica Morrison: 17:27 Well, it sounds very promising, what your team and yourself are doing. So–
A. Prof Pieter Eichhorn:17:31 Yeah. Hopefully fingers crossed.
Jessica Morrison: 17:33 Yeah. Fingers crossed. We'll talk to you and learn how it's all going. Pieter, what inspired you to become a researcher in this particular area?
A. Prof Pieter Eichhorn:17:43 Well, I was an undergraduate student in Canada at the time and I met someone called D.B. Weldon. And he basically said, "If you become a researcher, it gives you the opportunity to travel the whole world. You can work anywhere you want." And I went, "That sounds pretty good to me." So I randomly applied to do a PhD in England and I did a PhD on a syndrome – Cornelia de Lange syndrome – with these poor people that have a genetic mutation that really causes mental retardation and all these different malformalities. And after that, I moved to the Netherlands Cancer Institute in Amsterdam and I met someone called René Bernards. And he really basically showed me what the possibilities are of what you can really do on how to understand how the cells work and how that all relates to patients. And after that, I worked for someone called José Baselga who really, really showed me how the findings we have in the cells that we work in, in the institute, how that all relates to the patients.
A. Prof Pieter Eichhorn:18:46 And once you see that, the work that you've done inside the lab, and then you see a patient respond, where these women are living two, three, four years longer. You go, "Wow, this really makes a difference. What we're doing is really important." Right? And that clicked. I didn't have that when I was an undergraduate student, I didn't have that while I was doing my PhD. But all of a sudden you start working these things and you really realise that it really makes a difference. And so that's what sort of kept me going, thinking, "This is fantastic. I really like this."
Jessica Morrison: 19:21 And obviously, like you said, seeing those patients, these women live two, four, six years longer, must have really just been ...
A. Prof Pieter Eichhorn:19:29 Yeah. Just to show you that some of the things that we do, not just myself obviously, but the thousands of people that work on this are really making small incremental benefits to the treatment of these cancer patients.
Jessica Morrison: 19:45 Yeah, absolutely. Just lastly, a bit of a blue sky question. What do you personally think needs to happen in order to drastically reduce rates of breast cancer in the future?
A. Prof Pieter Eichhorn:19:58 One of the things that's really come out, and I'm not just talking about breast cancer, with all cancers, because a lot of the genes that are mutated in breast cancer are also mutated in ovarian cancer and prostate and brain, et cetera. So if we find a treatment for breast cancer that might also be applicable to other cancers as well. One of the big things that's coming out recently is we can sequence the individual tumours. So let's say a patient comes into the clinic that has breast cancer. We can extract that tumour and we can sequence it. And what I mean by "sequence it", is imagine that you have that cookbook in your vegetable drawer in your fridge. Well, we can read that entire cookbook, letter for letter, and we know exactly where all the spelling mistakes are.
A. Prof Pieter Eichhorn:20:50 So now we know what the spelling mistakes are. So imagine that patient came into the clinic and has a type of breast cancer called "Luminal A", which is usually a result of changes in oestrogen levels. So we give this woman tamoxifen and she has a fantastic response and she's cured. But 20 years later that cancer comes back again. Well, we know exactly what the cookbook was. We know exactly where those spelling mistakes were. And let's say [in] 20 years time, we have a new drug, but unfortunately that drug doesn't work too well and unfortunately that patient passes away a year or two years after that second treatment, but we know what those spelling mistakes were. Well, imagine if we now sequenced 1,000 women that came into the clinic and we know exactly what all their spelling mistakes are, and we know exactly 20 years from now, "Oh, this first woman came in and had these spelling mistakes. And [with] this treatment that we gave her she was able to survive an extra two years."
A. Prof Pieter Eichhorn:21:58 But we have the same woman that came in with those exact same spelling mistakes, but she received a different treatment and she was able to survive 10 more years. So we can use that knowledge of what all these individual spelling mistakes are, combine that to treatment. Now, imagine that wasn't 1,000 women – imagine that was a million. And we know all the different treatments that these women received over their entire lifetime, exactly how they responded to every single treatment. Now imagine 20 years from now, someone comes into the clinic and goes, "Oh, you have these spelling mistakes." We know from 20 years ago, this woman received this treatment and had the exact same spelling mistakes as you, but has lived 40 years or she's lived 20 years without any problems.
A. Prof Pieter Eichhorn:22:48 And that I find is the future. Really doing huge sequencing of all these different cancers, understanding the treatments they have and then going back and going, "Look, we can learn from all these patients that have come through the clinics in the past, and what's best for these women going forward." And that I find is the future. And there's some companies doing that right now where they're doing massive sequencing of millions and millions of cancer patients, correlating that to the drug treatments they've received and having that to understand the outcomes of these patients over time. And that will be hugely beneficial moving forward in the next 10, 20 years.
Jessica Morrison: 23:30 Thank you so much for coming in today, Pieter. Obviously, this is a hideous disease. It affects so many women and in turn affects so many lives. So what you're doing is really important and sounds like you've got some really positive things happening in your research and we wish you all the best. So thank you so much for coming and chatting with us today.
A. Prof Pieter Eichhorn:23:48 Thank you very much for having me.
Jessica Morrison: 23:50 This is the last episode of The Future Of that I’ll be hosting for a little while. I’m headed off on parental leave. While I’m certainly excited for what lies ahead, I’ll miss chatting with Curtin’s amazing researchers and learning so much every episode. In the meantime, you’ll be in the very capable hands of Sarah Tallier, who is a journalism lecturer here at Curtin University. Sarah is an experienced television, digital and radio reporter, who has worked for ABC News and commercial TV. You've been listening to The Future Of, a podcast powered by Curtin University. If you've enjoyed this episode, please share it. And if you want to hear from more experts, stay up to date by subscribing to us on your favourite podcast app. Bye for now.