One in two: a Manchester cancer research podcast

With one in two of us receiving a cancer diagnosis at some point during our lives, it has never been more important to improve the outcomes for people affected by cancer.

This cancer research podcast is brought to you by The University of Manchester in partnership with the Manchester Cancer Research Centre (MCRC). In each episode, our cancer researchers discuss the innovations, discoveries and projects that are changing the landscape of early detection.

Stream all available episodes below.

Episode one

Health inequalities with Professors Phil and Emma Crosbie: does going to communities directly improve screening uptake?

Profs Phil and Emma Crosbie

Professors Phil and Emma Crosbie discuss the early detection of lung and womb cancer, along with their work on community screening and addressing health inequalities.

With cancer incidence rising, particularly among the most socially and economically disadvantaged communities, the need for earlier detection interventions has never been more important. We find out how this cancer research power couple are transforming outcomes for patients through novel approaches to early detection.

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Podcast transcript

Sally Best:

Hello. You are listening to One in Two: a Manchester Cancer Research podcast, brought to you by The University of Manchester and the Manchester Cancer Research Centre. With one in two of us receiving a cancer diagnosis at some point in our lifetime, it has never been more important for our research to improve the outcomes for people affected by cancer. I am your host, Sally Best, and throughout this series I will be speaking with Manchester cancer researchers about their innovations, discoveries and projects that are changing the landscape of early detection.  In this episode, we speak to Professor Phil Crosbie and Professor Emma Crosbie about their research in the early detection of lung and womb cancer and their work on community screening and addressing health inequalities. With cancer incidence rising, especially amongst the most socially and economically disadvantaged communities, the need for early detection interventions has never been more important.

Phil and Emma Crosbie! Hello.  Thank you for joining me. How you doing today? 

Phil Crosbie:

Very well. 

Emma Crosbie:

Yeah. Really good. Thank you for asking us. 

Sally Best:

Oh, I'm great. Thanks for asking me. Oh, it's so great to have you both on. And, I mean, I'd like to get into the nitty gritty, but I mean, you're both a cancer research power couple. This is the term that we've coined, cancer research power couple. I love it, Phil’s shaking his head for those of you that can't see him. But I mean, we'll go with it. And I just like to start by asking how you both got involved in cancer research. And I'm going to come to the newly appointed professor Phil, kudos Phil. But yeah. How did you get involved? 

Phil Crosbie:

Well, I started from a clinical perspective, so I'm I started as a medical senior house officer doing post type ward rounds and seeing people come in as emergency cases. And the people with lung cancer were coming in with advanced disease. There was a shrug of the shoulders. We can't do much for them. Their life expectancy was days, weeks. And the messaging from senior doctors to junior doctors was this has been always the case. It's been like this for decades, and there's nothing we can do about it. And so then that represents a challenge and a challenge that I decided to try and address. So that was the journey for me. Um, I don't know about. 

Sally Best:

Yeah. 

Phil Crosbie:

Different from you. 

Emma Crosbie:

Yeah. Well, similar I guess. I was a junior doctor in training to become an obstetrician gynaecologist. And it was around about the time that, that scientists had realised that there was this very strong link between a virus and a cancer. And in my case it was human papillomavirus and cervical cancer. And I was fascinated by whether that represented any opportunities for early detection and prevention through vaccination. So this amazing opportunity came up to come and do a PhD here in Manchester with Professor Henry Kitchener and Peter Stern looking at HPV vaccination. And I just grasp it with both hands. 

Sally Best:

Oh, I love it. And is this is this how you guys met? 

Phil Crosbie:

No. 

Emma Crosbie:

Actually, in medical school together, we both went to University of Edinburgh Medical School. But I think when we first met. 

Sally Best:

Again, for the listeners, Phil’s shaking his head. 

Emma Crosbie:

I think, well, we worked, we were as medical students together in the same tutorial group. And I think Phil thought I was a bit square asking lots of questions at 4:00 on a Friday afternoon, and he wanted to get off and go and play rugby with his friends. So we didn't initially connect. But then when we became junior doctors together, we saw that we did actually get on quite well and I told him, it's up to you. 

Sally Best:

So I'm telling you it's great. We love it. We love that little insight. Phil doesn't love it so much, but there you go. You agreed to come on these things. Your life is open. So is it a coincidence you both ended up in prevention and early detection? 

Emma Crosbie:

I mean, yeah, I think probably so. I'm a gyno cancer surgeon, which essentially means that for me, the best outcomes for my patients is when we get the disease really early. And so looking at ways of preventing it from happening in the first place and detecting at its earliest treatable stage is an obvious way to improve outcomes for my patients. And I guess quite similar for you. 

Phil Crosbie:

Yeah. For me as a chest physician, you're involved in the sort of diagnosis and management of patients, not the oncological side in terms of chemotherapy. And the biggest impact I could have was on moving the diagnosis forward, and that was the area that I wanted to focus on to try to make the biggest difference. 

Sally Best:

Okay. And I'd like to pick up on that. So, I mean, would you be able to focus on the specific part of cancer prevention and early detection that you work in Phil? 

Phil Crosbie:

Yeah. So I mean, I had an opportunity to work at Wythenshawe Hospital to do cancer research and at that time there really wasn't any funding, any focus on lung cancer really as a disease at all because of its association with smoking. There was a sort of a blame culture. It's the individual's fault. All they have to do is give up. And that sort of fatalism had in a way, had gone through the whole of the sort of cancer community to mean that there wasn't any money or funding to try and make things better. But over the last few years, that has dramatically changed. I had the opportunity to get involved in an area where I thought actually that would make a big difference and therefore was able to complete a PhD in Manchester, which then gave me opportunities further down the line to have a role in cancer research and an increasing role in the sort of setting of screening and early detection. 

Sally Best:

And I'm wondering, like the, the emphasis was on early detection. And for my sake and for the listeners, would you be able to detail the importance of lung cancer, early detection? 

Phil Crosbie:

Yes, it's very straightforward. I mean, if you think of your lungs, they are to say two litres in size each. A lung cancer in its earliest stage. Maybe it's the size of a marble isn't going to cause any symptoms. There's a lot of area where it can grow and therefore for patients, by the time they develop symptoms, it's too late. The cancer has spread, they’re presenting the symptoms because it has spread to somewhere else say the bones or the liver and then it's an incurable disease. However, if you can detect a lung cancer early, it's curable. So if you identify, say, one centimetre lung cancer and if you have an operation, you have a 90% chance of a cure. Whereas the current state of play, because we're, you know, waiting for people to come to us with their symptoms, half of people, you know, die within a few months. At the moment. So you're completely shifting the disease through early detection from one that is often palliative to one that is completely curable. And that that intervention is really the only one that has such a dramatic impact. You need to find the disease early to cure it. 

Sally Best:

I'm very aware of kind of the landscape that you're working in, in the work that you're doing. But I mean, for the listeners, would you be able to explain the incentives that you're driving at the minute for detecting lung cancer early in certain deprived communities.

Phil Crosbie:

So the other thing with lung cancer is the close link with smoking. And smoking is the main driver of the development of cancer, lung cancer. In the UK smoking is also much more prevalent in more deprived communities. Um, so if you look at the distribution of lung cancer, the burden of lung cancer across society, there is a marked difference depending on where you live, whether your communities affluent, whether your community is more deprived. Um, and in our more deprived communities there is a huge amount more lung cancer. And that's especially the case in Manchester where we have some of the highest rates of lung cancer in the country. So the impact locally is huge and that's really the impetus to try and do something about it from our own local community. Um, so that association between smoking and deprivation is why you have the link between smoking and lung cancer, but you also have a link deprivation itself, the air pollution, occupational exposures.  There's a sort of a perfect storm of factors that come together. To me, lung cancer has a massively higher burden in more deprived areas. And therefore, any intervention you give, if you really want to make a difference, you have to be delivering that to the people who are affected most. 

Sally Best:

How are you delivering it, Phil? 

Phil Crosbie:

So well, in 2015, Macmillan came to Manchester and said, we want to make it. We want to do something, we want to make an impact on lung cancer. And so we sat around the table, a number of experts, patients, etc., around the table thinking about what is it, how do we make that difference? And then the concept, the design of the lung health chip. Then Kay was born and taken from scribbles on the back of envelopes in a committee meeting to actually designing a service where you implemented a screening service within deprived areas of Manchester. And the sort of design aspects of that were, well, we don't want people having to come to us, we want to take a service out to people so they're not having to worry about travel or parking or they don't have to come to hospital. We want to make our services accessible to everybody and especially to those who are in at most risk. And the intervention that actually saves lives for lung cancer is low dose CT scanning. So that's if you put someone at risk on a scanner, you've got a chance of detecting lung cancer and saving lives. And therefore, you have to take that's the intervention that you need.  And so you take that out to people and make it convenient, make it accessible. And that's what the lung health check approach is. The other side of it, of course, is you're not calling it lung cancer screening, you're calling it a lung health check to reduce any sort of perceived anxieties associated with lung cancer. So if you imagine if you live in a community where there's a lot of lung cancer, almost everybody you will know who was diagnosed with. Lung cancer has died of it. Therefore, the fatalism around that is also something you have to try and address. And hopefully as we do more and more screening, we can then inform people and say no laterally, this is a curable disease. We can do something about it. 

Sally Best:

Yeah, I mean, it sounds great and I think it's kind of detracting from the ignorance is bliss perspective that I think a lot of people may take with screening and things. And I mean, just to reiterate, so you're addressing the challenge of socio economically deprived communities that have high prevalence of kind of late stage diagnosis. And what you did was put kind of vans in car parks and deprived areas and then people would come for that long health check and you'd kind of do routine follow ups if there was any progression or kind of a late stage or early stage. Cancer is that right? 

Phil Crosbie:

So, well, what you're doing in the lung health check is, it's actually a bit more holistic than purely lung cancer screening. So the other things that we tagged on to it to make it more like a lung health check with things like a breathing test to look for COPD, which you get with smoking. We have smoking cessation practitioners on the truck again for prevention of not just cancer but diseases associated with smoking as well as an assessment of lung cancer risk. And then those individuals who are high risk are then there's a CT scanner immediately next door to where that lung health track takes place. And you go on and you have your scan and the whole thing takes 20 minutes. So that that part of the service is it's literally about 20 minutes. It's very quick for people, very convenient. And then the data, the information that's collected is then brought into the hospital where it's looked at by specialists. And then those CT scans are read by specialists. And if you have a lung cancer, then you are immediately brought into a hospital to have tests and diagnostics done. If you don't have lung cancer or a concerning finding, then that's the person's informed and then further scans are arranged. So that's the sort of set up.

Sally Best:

Great stuff.  And I mean, my next question will be, what's the success been of this so far? 

Phil Crosbie:

So, well, you can judge that in a couple of ways. One is in terms of lung cancer. So we've had a pilot about five years ago now where one in 23 people who stood on that truck and had a scan were diagnosed with lung cancer. 80% of those had early stage curable disease. Nine out of ten were offered curative treatment. And that's because they had stage one, stage two disease, whereas normally people are coming to us with stage three, stage four incurable disease. So just standing on a truck means that you completely change the stage of presentation of lung cancer. You change it from a terminal disease to a curable disease simply by something on a truck in a carpark. So that was a profound thing to see. And as a clinician sat in a clinic with a patient opposite me, I remember it distinctly looking at somebody and going through the questions you do for assessment, but thinking in my mind, if you hadn't stood on that truck, then we may have been seeing you one year later or two years later with I'm having a very different conversation, so it has a profound impact on you in terms of the other things that we, you know, offering people smoking cessation, early detection of COPD, etc.. They also come in with the service as well. So Manchester really drove this the innovation, the implementation of the lung health track started in Manchester and then from that it's been adopted nationally through NHS England. NHS England have backed it and said, right, we like this, we want to do more of it and funded a targeted health check programme initially at about ten sites, but now there's 29 sites or so. And indeed the UK National Screening Committee is deciding whether to roll it out nationally. So the impact from, you know, what we started here in Manchester could have a profound impact across country and indeed beyond. 

Sally Best:

And fingers crossed for that funding. I mean, it's great to hear about this work focussed on cancer outcomes and underserved communities because I think that's kind of a large area of poor health and it's great to hear that you're directly addressing in lung cancer specifically. I mean, Emma I'd like to come on to you and some of the amazing work you've been doing on HPV. I'm wondering if you've been able to talk about this specific part of cancer prevention and early detection around HPV and cervical pre-cancer? 

Emma Crosbie:

Yes. So we now know that cervical cancer is caused by persistent infection with high risk human papillomavirus, or HPV. And this is really exciting. This understanding, because it enables us to both prevent HPV associated cervical cancer by vaccination. So that is by vaccinating all teenage boys and girls with the HPV vaccine, which then prevents them from ever getting infected with the virus in the first place, and so effectively prevents them from developing cervical cancer in the future. But also because of this strong link and because it is so intimately associated with cervical cancer, we know that it is a really good biomarker for screening. And what we mean by that is that we find evidence of that virus before the patient goes on to develop cancer. So we see it just as an asymptomatic infection, we see it in people who've got cervical pre-cancer and we see it in people with cervical cancer. And the importance of that is that it's actually quite a long period between becoming infected and developing a cervical cancer. And if you can screen that person for HPV during those years of infection, you have the opportunity to find pre-cancer cells, which you can then treat and again effectively prevent the person from ever developing cancer. So it's understanding the biology underpinning this link between HPV and cervical cancer. That's so exciting because it does offer the opportunity to completely change outcomes with respect to cervical cancer. So in countries where they don't have organised screening programmes and immunisation programmes aren't universally funded, you know, they have a huge burden of cervical cancer, often affecting young women, women in their thirties, forties and fifties. And it's really a terrible disease when it's picked up in its later stages, you know, with often terrible numbers of deaths and illness from the cancer. So, you know, we're in a fantastic place here in the UK to be able to screen and prevent cervical cancer through understanding about HPV and the link. 

Sally Best:

Okay. And I know you've been working on alternate screening methods, and I'm wondering if you be able to tell the listeners a little bit more about that. 

Emma Crosbie:

Yes. So we as you know, cervical screening has traditionally been carried out by a woman going to see her nurse in the general practise and having a speculum examination and having a sample taken directly from the cervix. And in the past that was then looked at under the microscope to look for cervical pre-cancer cells. But now we've moved to testing that sample first for high risk HPV, and only if it's positive do we then look at it under the microscope to see that the person is genuinely at risk of cervical pre-cancer. And because we know that this HPV is so intimately associated with cervical cancer and also that, you know, skin cells are shed naturally during just normal life, the cervix sheds its cells and they contain HPV in them that you might be able to actually use a slightly less invasive method of picking up HPV from the lower genital tract. So initially there's been a lot of work looking at vaginal cell sampling, which is where the woman collects a vaginal sample using a swab in the privacy of her own home, which she then sends to the laboratory for testing for HPV. But here in Manchester, we've been interested in looking at whether urine could do the same. In other words, whether we could test a urine sample for high risk HPV, and if that would be as accurate as collecting a cervical sample and testing it for HPV. And so some work that we've been doing here in Manchester is looking at patients who we know to have an HPV infection when they come to the hospital to look for cervical pre-cancer and taking matched samples from the cervix alongside a urine sample. And just comparing the accuracy with which those two sample types detect HPV in those who've got cervical pre-cancer. And so far, the results are really, really exciting. To the extent that we think that a urine sample is not inferior to a clinician obtained cervical sample for the detection of HPV. And the reason why that's so exciting is because, of course, women don't really like having a speculum examination and having a routine cervical sample. The evidence suggests they're not really that keen on taking a vaginal self-sample either. But women are very used to collecting urine samples for all kinds of reasons, and we think that this might be a much more acceptable way of collecting a sample to find out if somebody is at risk of cervical pre-cancer. 

Sally Best:

I mean, it's amazing. Again, because it's the accessibility angle that both you and Phil pioneering here on. I mean, I want to ask again, in terms of socioeconomically deprived communities, do we see less take up of screening specifically in those communities? 

Emma Crosbie:

Yeah, absolutely we do. So on the one hand, people from socioeconomically deprived communities are at greater risk of cervical cancer because they are often smokers, but also because they are less likely to go for cervical screening. So as we spoke about before, there is a long time period between becoming infected with HPV and developing cervical cancer. And so if you are a person that goes routinely for cervical screening, then there are many opportunities to pick up that infection and those cervical cancer cells prior to the development of cervical cancer. But if a person doesn't go for cervical screening, then those pre-cancerous changes are not identified and they are not treated, which means that they are at risk of developing cervical cancer. So it's both the fact that they are often smokers, but also the fact that they are less likely to go for screening that puts people from socioeconomically deprived communities at increased risk of cervical cancer. 

Sally Best:

Okay. And I'd like to come on to that kind of two pronged approach in a bit. But I mean, can I just clarify that the challenge you're trying to solve in cervical cancer, early detection is kind of the same as Phil. So it's detecting early where outcomes and prognoses are improved. 

Emma Crosbie:

Absolutely. That's right. And specifically trying to address the barriers that we think are really important for marginalised groups that don't traditionally attend screening. 

Sally Best:

Okay. Fab, I mean a question for both of you. Again, it's what encouraged you both to focus on cancers in deprived communities. Was it kind of one of those things that it was just so happened that the cancers that you were focussing on did have the angle or was it specifically, Phil you've spoken about this before, but was it specifically I want to help in terms of health disparities, addressing health disparities? 

Phil Crosbie:

That's why it's both. I mean, but for lung cancer, the connection is so stark that if you don't, you don't make the big impacts that you need to do, but they go hand in hand. And so I suppose both from a clinical service perspective, you have to make sure your service delivers to people who need it most. But also from a research perspective, you still have to make sure your research is actually the results that you get from your research are generalisable to the people who also get lung cancer. So one of the factors that we're trying to do in Manchester is also take our research out into communities as well, because the barriers that exist for services in accessing screening of the same barriers and probably worse actually for research. So if you have a research that looks at, say, lung cancer screening and the majority of people taking part are not really representative of the people who get lung cancer in your community, then that means that the results are not necessarily as generalisable. So the push more recently has been to try and break down the barriers to research participation as well, because that's really important, because the results we get, we want it to be generalisable to people more broadly. 

Emma Crosbie:

Yeah. And for cervical screening, you know, we know that people who are from more affluent areas are much more likely to go for routine screening. They're much more likely to have been immunised as preteens. And therefore you have this situation whereby the worried well, who are those people who go for screening and vaccination programmes are doing extremely well from the services that are available here on the NHS, but those that have poorer access to those services just get a really bad deal in terms of much more likely to be diagnosed with cancer, much more likely to have bad outcomes. And so it is addressing that health disparity and trying to make it much more even for the whole population so that everybody can have good outcomes. 

Sally Best:

There's a lot of overlap between both your research areas in terms of prevention and early detection of cancer. And you both have this focus on addressing needs in underserved communities. It kind of makes me want to ask and I kind of know what the answer is going to be. But I mean, does the fact that you both work in the same environment make it easier for you to collaborate on projects? 

Emma Crosbie:

Yeah, I would think so. 

Sally Best:

Yeah. Is this dinner time talk? 

Phil Crosbie:

Yes, of course. 

Emma Crosbie:

Yes. And so, I mean, that is something that we probably going to talk about just now. But yes, I mean, noticing that the cancers that we're interested in do seem to affect a similar population demographic, it's clearly of interest to us because it was like, well, if you're tackling these disparities using your lung health check in socioeconomically deprived communities, is there a way that we could also harness that fantastic service to try and take cervical screening to the same community? So that was really a teatime discussion, I think. Yes. 

Sally Best:

Your dinners must be amazing. Solving world health issues blimey we just get on to the why have we got boiled potatoes and not roasted? I mean, but anyway, you've led me on Emma. So are there any projects you're both jointly working on? 

Emma Crosbie:

Funny you should ask that. 

Sally Best:

Funny, I thought. Yeah, as if I know.

Emma Crosbie:

Yes. No, we are. We've started an initiative called the Moped Initiative, which is the mobile cancer Prevention Early Detection Initiative, which is essentially, as Phil says, taking cancer research to the communities that need it most. And in the case of lung cancer and cervical cancer, that is communities from socioeconomically deprived backgrounds. And so because of the success of the lung health check, whereby people from those backgrounds are actually attending for lung health checks on lung cancer screening, we decided that that might be a really great opportunity to also look at whether we could offer our new urine HPV test to people attending that lung health check. So in other words, could we do a so-called one stop screening shop for both lung cancer and cervical cancer? And so that is a research initiative that we are very excited as just got started and it is using a kind of a research room at the back of the lung health check, which is the clinical service. 

Sally Best:

So is this just in Manchester at the minute? 

Emma Crosbie:

Yes, it is. 

Sally Best:

Okay. Paint me a picture of what is going on inside these trucks. We've got a CT scan for Phil’s stuff. Yeah, well, what else have we got? How many people are in there?

Phil Crosbie:

Well, it's quite a I mean it's quite an industry, but it all fits together with the logic of essentially trying to address things in a one stop shop model that are, you know, if you if we're sort of saying that we have underserved communities that aren't accessing services or getting the health benefits from the NHS or whatever, then trying to address that and, and doing so in a way that's acceptable. So we don't overburden people. But actually the feedback has been fantastic actually from everyone attending. When you go on the truck, the atmosphere is great and people do appreciate just having these various things checked. So you see there's a flow there's a flow to the truck where you have you see your lung health check nurse who describes what's going to happen. There's a room where you go, if you're a smoker, you go and see the smoking cessation practitioner. Then the research team is next. And it's not viewed as I think this is this is a great credit to the clinical service. Actually, research is not viewed as an added extra. This is fully integrated within the flow of the truck that you're going around these rooms. And obviously that has to go in each room. But these rooms are there. There's a flow and then you have your scan at the end and off you go in to your shopping if you wish to all go home. So the whole thing is very well integrated. It's a great atmosphere and, and the feedback we're getting is really good. But, but what we're trying to do is deliver all these potential health benefits to people in a convenient way and why not try look for the malignancies in the same way that we're trying to look, say, for COPD or indeed trying to help people with the smoking. So it's all part of that same package. 

Sally Best:

But where did you find your TARDIS?

Phil Crosbie:

Oh, there are there's two big trucks with the lung health check team in them and also a mobile C.T. scanner. So it is a big set up and the logistics of it are significant, but it's certainly worth it. 

Sally Best:

So Emma, where do you come in to this kind of flow? 

Emma Crosbie:

So in the research room, obviously, I'm really only interested in targeting people with a cervix, mostly women, and we are asking those women when they are, you know, if they're interested in taking part in research, whether or not they have routinely been for cervical screening in the past, and if they might be interested in having a cervical screening sample taken in the form of a urine test. And we are targeting women over the age of 65 who have exited the cervical screening programme. So we're not interfering with the NHS cervical screening programme. So this is really trying to identify those who haven't attended NHS cervical screening, and that's mostly because cervical cancer actually has the poorest outcomes in terms of contracting the disease and dying from the disease for women in their seventies. And currently we stopped screening at 65. But if people haven't been screened, as I said before, then they haven't had a cervical pre-cancer treated, which means that they are at risk. And so it's trying to find out whether those women who haven't been for routine screening, perhaps because they didn't want to have a speculum examination, might be interested instead in giving us a urine sample. It's just a very small urine sample collected using a little device called the Collip, which reliably collects the first fraction of urine that a woman passes, and then sending that to laboratory to be tested for HPV in the same way. So taking part in our study is actually quite a short thing, but we're hoping to get lots and lots of patients agreed to take part so that we can see whether or not this could be a successful initiative to be rolled out. 

Sally Best:

And I'd just like to emphasise to the listeners, this is in carparks, you would have never of thought it. Both of you, what's your hopes for the future of this incentive? Rolled out nationally?

Emma Crosbie:

So I think for me it's kind of reappraising the age at which we stopped screening. So other countries, for example, Australia, Denmark, some of the other Scandinavian countries, they actually stopped screening for cervical cancer at 79. But here, perhaps for historical reasons and perhaps because the test is uncomfortable in a postmenopausal woman, we stop at 65. So it's really sort of examining that and with fresh eyes and saying, should we be stopping at 65? Is there something we can do for women who are older than 65 and, you know, could urine be a reasonable alternative? Do women who haven't been screened before, particularly those from socioeconomically deprived communities, do they prefer to collect a urine sample for cervical screening and is a one stop screening shop something that they'd be interested in? 

Sally Best:

And I mean, are you kind of looking to integrate? I mean, it's already a TARDIS as it is but I mean, it seems never ending. So are you looking to integrate other cancers into this one stop screening shop? 

Emma Crosbie:

Yeah. 

Sally Best:

Copyright on that by the way 

Emma Crosbie:

So, I mean, it's about targeting your screening to the right people. So, you know, obviously breast cancer screening is it tends to be in a slightly you know, it occurs in a different way. You know, you need mammography, you need ultrasound services, you need biopsy services and so on and so forth. And, you know, that's not really the same demographic of individuals that are at greatest risk of lung and cervical cancer. So it's about being smart about what screening bundle you offer. But there certainly are other cancers that are things that we should be considering. If this is successful. 

Sally Best:

Which I'm sure it will be, I have all the hope and a personal question again. But I mean, you're both cancer researchers and you both have kind of many hats that you wear. How do you how does it feel that you're in a fast paced environment? How do you deal? I mean, you've both got three kids and a dog and two cats. I'm sorry you all missed this preamble, but that's the bits that I love. How do you balance it all? How do you find that? Do you kind of feel like you're going to break down into a heap at some point? I mean Phil, you're very slow. Like not slow. You're very steady like the world. 

Phil Crosbie:

I think it's the same for every family, isn't it? You've always got time pressures too much to do when you just have to go do the best you can each day and every day. And actually it helps in a way to have being the same in sort of research environment, because the conversation we have a very you know, we have a debrief where we maybe walk the dog or whatever, having a chat about the day's events and then that just sort of is put to bed and then we deal with the day to day with the kids and what's needed. I don't think it's any different to any other busy family that particular. 

Emma Crosbie:

No, I think so. But we are both very, you know, driven. And I think if we weren't so passionate about what we did, you know, perhaps we wouldn't manage to balance it. But it's that it's that drive to really make a difference for our patients that's kind of fuelling this fast moving, exciting time in our lives. 

Sally Best:

Yeah, that dog must get over walked. You're discussing debrief from the day. Jeez, I feel. I really feel for him. It's like he'll be falling off by the end of it. I mean, it's it's another personal one, but how does it feel to know that you're both benefiting the lives of cancer patients and also kind of cancer patients that are from these economically and socioeconomically deprived communities? 

Phil Crosbie:

I mean, to deliver research that has an impact is it's I mean, it's a fantastic area to work in. It's motivating. I suppose you'd never satisfied that what you've done is good enough. And you always are looking for ways to keep making innovations and improvements. But when you do pause and think actually, yes, it has that impact is a really good feeling. But no you never you never sort of panic self on the back particularly and go great jobs done you then moving on to the next thing to go how do we get better or I mean you're constantly looking for ways to improve what you're doing. That's my angle anyway. 

Emma Crosbie:

Yeah. I mean, just totally driven by the desire to make a difference for our patients. And I'm constantly striving to tackle the next hurdle that we see. So it's, it's not a journey that has ended or feels like it's ending any time soon. It feels like a long, winding road that we are enjoying the journey of. But yeah, lots more challenges ahead I think. 

Sally Best:

Yes. I mean, there's so much more to come from you both. I am so sure we'll have you here in another month talking about something different. Have you got any titbits, any secrets, anything in the pipeline we can be looking forward to? Emma’s got a cheeky look on her face. 

Emma Crosbie:

Well, you know, are looking at the urine test in all kinds of different scenarios. So looking at different groups of people who may not have been for routine screening in the past. So that's exciting to see if there are ways of addressing more than just this socioeconomic deprivation issue. But, you know, perhaps we could appeal to other groups of people who perhaps haven't been screened before. So, yeah, definitely watch this space. 

Sally Best:

Phil, in terms of your mopeds, what do you want to come out of that? 

Phil Crosbie:

I think it's just for there to be an acknowledgement that research has to be representative of the people in our society. And we need to have because the results we generate, the data we generate has to be of benefit to everyone and not just to a select few. And I think that's an important, you know, whether it's by physically taking research into a car park or whether it's simply saying, actually, we need to try and be mindful of this issue and try and overcome it. And I'm sure there are various different ways of doing that, but it's just an important issue that we should be addressing. That's the key, I think, to it. 

Sally Best:

God, you've got the key and the secret if you got that reference. Honestly thank you so much, both of you, for speaking to me today. I know you've got absolutely hectic schedules and it's so appreciated because we get to speak about all this amazing stuff. And yeah, you're a cancer research power couple and there's there is no other term for you. Yeah, I might even have a picture of you on our wall at work. As the gods. But yeah, I hope as well I'll be speaking to you in the near future about this work because it's just it's incredible. And I think the pace that it's moving and people saying that it needs funding and things is incredible. But I mean. Yeah, just. Thanks again, guys.

Emma Crosbie:

Well, thanks for having us. Thank you for having me. It's been fun. 

Sally Best:

Oh, it has been fun, hasn't it? And thanks again for the listeners I’ll link Phil and Emma’s work in the blurb because there's a lot of stuff that we have written about because yeah again power couples, they need that air time so thank you for listening to us and yeah see you next time. If you have been affected by anything you've heard in this episode, please see the show notes for our list of charities and organisations that can help. 

One in two to was brought to you by The University of Manchester and the Manchester Cancer Research Centre. Listen to our next episode to hear from more of our researchers as they share the innovations, discoveries and projects that are changing the landscape of cancer prevention, early detection and treatment. To find out more about what you've heard today, please see the show notes for this episode, where you'll find a transcript and links to further information and research. 

Cancer is one of the University's five research beacons, showcasing the interdisciplinary collaborations and cross-sector partnerships that are tackling some of the biggest questions facing the planet. To hear more about Manchester's research in advanced materials, biotechnology, cancer, energy and global inequalities, go to Manchester.ac.uk/beacons.

Related research papers and resources

Speaker profiles

Professor Emma Crosbie  

Emma Crosbie is Professor of Gynaecological Oncology at The University of Manchester and Manchester University NHS Foundation Trust. She is also the lead for the cancer prevention and early detection research theme at the NIHR Manchester Biomedical Research Centre. Her research interests include screening, prevention and the early detection of gynaecological cancers, as well as developing new treatments and interventions for women with established disease.  

Professor Phil Crosbie  

Professor Phil Crosbie is a Senior Lecturer in the Division of Infection, Immunity and Respiratory Medicine at The University of Manchester and an Honorary Consultant in Respiratory Medicine based at Wythenshawe Hospital, Manchester University NHS Foundation Trust. His research and clinical focus is the early detection of lung cancer. 

Episode two

Breast cancer with Professor Gareth Evans: should all women be screened equally?

Prof Gareth Evans

In this episode* we speak to Professor Gareth Evans about the importance of breast cancer screening, as well as the risk predictors of breast cancer.

Gareth discusses risk prediction, early detection and prevention of breast cancer, highlighting the outputs of trials led by Manchester to investigate the best routes for breast cancer screening. 

*Please be aware, this podcast was recorded on Tuesday, 7 June 2022, when Sajid Javid was still Secretary of State for Health. 

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Podcast transcript

Sally Best:

Hello. You are listening to One in Two, a Manchester Cancer Research podcast brought to you by The University of Manchester and the Manchester Cancer Research Centre. With one in two of us receiving a cancer diagnosis at some point in our lifetime, it's never been more important for our research to improve the outcomes for people affected by cancer. I am your host, Sally Best, and throughout this series I will be speaking with Manchester cancer researchers about their innovations, discoveries and projects that are changing the landscape of early detection. In this episode, we speak to Professor Gareth Evans about the importance of breast cancer screening, as well as the risk predictors of breast cancer as he answers the question, should all women be screened equally for breast cancer? So today I'm speaking to Gareth Evans. Would you be able to introduce yourself, Gareth?

Gareth Evans:

I'm Professor Gareth Evans. I'm a consultant in genomic medicine, but also I'm Chair of Cancer Epidemiology and Medical Genetics at The University of Manchester.

Sally:

Fab Thank you. So I guess we'll get started. So we've heard from that that you focussed on early detection of breast cancer as well as breast cancer risk factors. And I'm wondering if you could please start off by telling me and the audience why is it so important to screen for breast cancer?

Gareth:

Well, breast cancer screening is important because it's able to detect breast cancer at an earlier stage, where cure is more likely. And we know from a lot of information on breast cancer that the earlier the stage, the better the cure rates from those stages. So, for instance, stage one is below two centimetres in size with no involvement of the lymph nodes. And those patients detected at stage one do much better than those at stage two and those that where the cancer is spread beyond the breast itself. So the idea of breast screening is to detect breast cancer early. Now, no screening is perfect, so no screening will detect all cancer and have no false positives. In the UK we do three yearly screening from the age of 50 through to 69. In most other organised screening programmes, it's two yearly screening and sometimes that starts at 40 rather than 50. The reason that screening before 50 is more problematic is because the incidence is much lower, so only about 20% of breast cancer occurs before the age of 50 and the cancers grow faster and the breast tissue is more dense, which means that you have to actually do the screening more frequently. So from a health economics perspective, it's not cost effective to the NHS to do that screening on everyone below the age of 50.

Sally:

Okay, so you've said that there are occurrences of some women below 50, and I'm just wondering, would you be able to explain how some of these women are referred for early breast cancer screening?

Gareth:

Yes. So there is a facility for some women to get screening earlier if they meet certain criteria that are specified by NICE. That's the National Institute for Clinical Excellence. And that is if their family history of breast cancer is sufficient for them to have that early screening. And so a typical moderate risk woman would be someone who's got a mother or sister diagnosed under 40. And a typical high-risk woman would be someone who's got a mother and sister, both diagnosed before the age of 50. And in those situations, a moderate risk woman would get annual screening from 40 to 50 years of age and be considered for annual screening between 50 and 60. And a high-risk woman would get screened from 40 to 60 every year. Now there is an exceptional group and that is those that are proven to carry faults in the main high-risk genes, BRCA one and BRCA two. They have lifetime risks of up to 80%, eight in ten of getting breast cancer. And they qualify for the very high-risk screening programme, which is essentially annual screening from 30 to 70, but includes MRI scans of the breast, which are much more sensitive than mammograms, particularly where there are dense breast tissue present, which is typically the case in younger women. And they can sometimes even qualify for screening before the age of 30, depending upon other risk factors. So that is a tiny group. The high-risk group are based on the NICE criteria is only about 1% of the population, with about another 3% being in the moderate risk groups, a maximum of 4% of the population can present to their GP's with their family history and get earlier screening. In reality, less than half of those women actually do that.

Sally:

Okay, so you've mentioned the women that have the BRCA one and BRCA two. I'm just wondering if there are other genetic risk factors that increase your risk of developing breast cancer who aren't identified by these hereditary clinics?

Gareth:

Yes. So there are additional genes, although they contribute much less to the situation because they are rarer or are not high enough risk. So there are other high risk genes, including a gene called PLB2 and TP53, and they would also qualify for that very high risk screening. And then there is a group of moderate risk genes which roughly double to treble the risk giving you a rough 20 to 30% lifetime risk, they wouldn't qualify you for more than moderate risk screening without a significant family history. But additional to those, and much more important on a population level are what we call polygenic risk. So the individual genes, you just have a genetic fault in those that can increase your risk. But that is less than one and a half percent of the population. So less than one in 70 women in the general population carry one of those type of genetic faults. But many more of the population can carry common genetic variants which, when taken together, push your risk right up. So it's like a pack of cards. You get your single nucleotide polymorphisms, these common genetic changes, one set from your dad, one set from your mum. If you get the wrong deal of the cards, your risk can be high. If you get the right deal of the cards, your risk can be low. And about 50% of the population can get a meaningful change in their risk on the basis of a polygenic risk or from these common genetic variants, whereas actually on a population basis, only about 1.3, 1.4% of the population would get a meaningful result. In other words, a positive test result from a BRCA one or a BRCA two gene fault or one of the other rarer genes.

Sally:

And just for the benefit of our listeners, I'm wondering if you'd be able to describe what is a polygenic risk score and if you have any analogies that would be able to encompass a risk score for women for breast cancer.

Gareth:

So what we do in a polygenic risk score is we assess genetic changes called single nucleotide polymorphisms. So these are literally just a single letter change in the genetic code. And these may be in genes or they may actually be between genes. So they don't have to be an actual change in a gene. And at the moment, we're using scores of up to 313 of these genetic changes. Now, some of these changes may increase the likelihood of breast cancer slightly. Some may reduce them. So individually, they're of no real benefit. But when put them together, you can end up with a risk which is three times the average, or a risk which might even be three times less than the average. And it's a bit like, as I said, getting a deal of cards. You might get a fantastic handful of aces and kings. That means that in poker or in bridge or whist, you're going to win the hand. So you're not going to get breast cancer because you've got such a strong hand. You might get a terrible hand, which means that the likelihood of you getting breast cancer substantially increases. And every time you shuffle the pack, you will get a different deal from the two parents that have their children. And that means that the polygenic risk score can be substantially different from parent to child or even sister to sister. So, for instance, I've seen two sisters, one of whom had a twofold increased risk, doubling of her risk. The other sister had a halving of her risk. So those sisters had a fourfold difference in their risk of developing breast cancer, which is an enormous change. That isn't because one had BRCA one and one didn't. It's because their polygenic risk score was substantially difference between one and the other. The important thing about this is that we identify this very low risk group, which doing the standard gene testing for BRCA one and two doesn't give us. Being negative or having no fault in those genes does not really reduce your risk unless you've got an incredibly strong family history. So there is very little benefit of a negative test for all of the moderate and high risk genes. BRCA one, BRCA two, etc. But there can be huge benefits from doing a polygenic risk or in terms of identifying women at very low levels of risk.

Sally:

Yeah, it's really interesting how I mean, I'm quite surprised. I don't know if the listeners would also be surprised about that variability between family members and risk. I was under the impression that it was kind of a a continual spectrum of your mother was at high risk you're at high risk. Your sister's at high risk you're at high risk. And I guess it's interesting to hear, but I think it also highlights the importance of screening to differentiate between even family groups. So just kind of leading on from this genetic risk side of things, your research looking at saliva tests for breast cancer has recently been spotlighted in the Times and the Daily Mail and also in Julia Bradbury's documentary Breast Cancer and Me. And it's been described by Health Secretary Sajid Javid as promising new research. And I'll put the links in for the listeners that are interested, they're kind of very good reads. But I wonder if you'd be able to tell me more and tell the listeners more about this research and the results of this recent study.

Gareth:

So what this study does is it brings together all of the known risk factors. So what we call standard risk factors, those are things like when your periods start, when you have your first child, how many children you have, when you have your menopause, taking HRT, etc., your BMI. In other words, your weight and particular weight gain is the most important thing. And it takes together those standard risk factors that can put be put together in a risk tool with two actually much more predictive factors. And those are the polygenic risk score which I've just described. And breast density. And we now know that the bottom, you know, 10 to 15% of the population has a risk, 5 to 6 times less than the top 10 to 15% of the population based on assessing the density of the breast tissue on a mammogram. Now what we're looking for is on a mammogram, the white areas which represent the glandular breast tissue and fibrous tissue, and that is the risky tissue. So the less of that you have, the less risk there is, the more of a risk you have, the more risk there is. The other factor with breast density is that it can mask your breast cancer. So there are two elements to the risk. One, it's a higher risk that the mammograms won't pick up your cancer early, but also it's a higher risk overall that you'll get breast cancer. Now, we can now put all of those three factors together to come up with a ten year risk and a lifetime risk of getting breast cancer. So we can really accurately risk stratify the population into low risk groups, which have a very low risk of breast cancer and high risk groups which have a very high risk of breast cancer. Not only that, a higher risk of cancers that are likely to be later stage. So not so easy to pick up on screening, which means we need to do the screening more frequently. And so what we've shown in the study is that we can identify about 20% of the population who are in these moderate or high risk categories. That is a ten year risk of 5% or greater in the screening age group, 8% or greater for the high risk group. And those 20% develop nearly 50% of all the stage two cancers. So by identifying that group, we can potentially down stage half of all breast cancers, but also potentially prevent those breast cancers by those women taking medication or doing lifestyle factors which will help reduce their risk.

Sally:

I'd like to touch on that in a bit, but I know that you've been working on risk stratified screening and in particular cities such as PROCAS one and PROCAS two. And I'm wondering if you'd be able to provide a bit of a background to those studies, what they've been looking at and then how they differ to this one size fits all screening that we currently see in the NHS.

Gareth:

So what we've been doing is looking at really the whole totality of the risk and we know that for instance, lifestyle factors do affect the risk. In particular it's weight gain. So the more weight you put on from your sort of early adult weight at age 18,20, the more of that increases particularly your postmenopausal risk. So the risk after your menopause, which is typically 51, 52 years of age, when the periods have stopped, and that is the main period of risk. So over 80% of the breast cancers occur in postmenopausal women. And what we've been able to do is look at the risk factors, also look at, as I've said, breast density and the polygenic risk scores. And this allows us to really accurately divide up the risk, also to be able to advise women who are at most risk that they can reduce their risk, if they've gained weight, by losing that weight. We're not trying to get women to go back to weights below they were when they were 18 or 20 but if they can approach the weight when they were 18 or 20, that will very substantially reduce their risk if they put on a loss of weight and so these are factors that we can use in that. Now, in terms of the risk stratification at the moment, as we said, nearly every woman is offered screening only three yearly from the age of 50 and probably only about one and a half to 2% of the population come forward because of their family history and get more frequent screening before the age of 50. What we've shown is if we were to do a risk assessment at say age 30, we could detect 9% of the population at high risk and about 11% of the population at moderate risk. Who would qualify for that early screening. So we would increase the proportion of women eligible for that early screening by about tenfold, and we would have a much greater impact on picking up breast cancer early. Not only that, we would do more frequent screening for the women at high risk. So 9% of the population, one in 11, between 50 and 60 down staging potentially those cancers. There may even be a case for more frequent, maybe two yearly screening in the moderate risk women. And there may even be a case for reducing screening. May be starting it a bit later in women at very low levels of risk. So by combining all of these measures, we can very accurately risk stratify. And the important thing in the low risk group is that there is a much higher rate of effectively over diagnosis. So cancers that may never present clinically being a higher proportion of their overall cancers. But not only that, that their likelihood of developing a stage two cancer is much lower. So potentially the overdiagnosis, the overtreatment of these women, the fact that they're getting more biopsies when they haven't got cancer are things that are downsides of screening, which can potentially balance much better the risks and benefits. So more frequent screening in those at higher risk, maybe slightly less frequent screening in those at very low risk, but may be starting their screening a bit later. And these are things we're exploring with women themselves who are identified that they are at low risk.

Sally:

Okay. So you've talked about women that are identified at higher risk. They can take precautionary measures such as kind of looking at their BMI and then having this increased screening frequency. I'm just wondering if you'd be able to talk about the preventative medication side of things and how that links into some of the studies that you've done.

Gareth:

So there are now three medications that can be taken to reduce the risk of breast cancer, the most commonly used and commonly known is called Tamoxifen, and that is a treatment that's been used for over 40 years in women with breast cancer. It blocks the oestrogen receptor on the breast tissue, and that has been shown to significantly reduce the risk of breast cancer in women with breast cancer in their other breast, that unaffected breast. But also in clinical trials, it's reduced the risk of breast cancer by about 30 to 40% in women who don't have breast cancer in the first place. So it is now recommended for NICE, particularly for women before the menopause. After the menopause, there are two additional drugs that can be used, and these are Raloxifene, which is also a blocker of the oestrogen receptor, but has a few less side effects than Tamoxifen, but unfortunately isn't quite as effective at prevention. And then there is Anastrozole, which is an aromatase inhibitor, and that drug actually stops you producing oestrogen after the menopause. You do produce oestrogen from your fatty tissue and your adrenal glands, and it's able to reduce that level that's produced. So Anastrozole is even more effective and Tamoxifen, reduces the risk by about 50% and also has less side effects. The important side effects that Tamoxifen potentially has that make it less suitable after the menopause is it increases the risk slightly of getting cancer of the lining of the womb, whereas Anastrozole does not do that and there's a slight increased risk of blood clotting and Anastrozole has much less of an effect of that. So overall, although there are some side effects with these medications, they are very, very effective at reducing risk. And NICE recommends offering these treatments Tamoxifen to pre-menopausal women, Anastrozole to postmenopausal women who are at high risk and considering them for women at moderate risk. And NICE has shown in a health economic assessment that actually taking Anastrozole because it's so inexpensive, about two or three pence a day is actually cost saving to the health service because the treatment of cancer is so expensive that actually stopping those cancers occurring saves the health service a huge amount of money. But I think as importantly, if not more importantly, saves women the hassle of going through a diagnosis and all of the treatment that's involved in a breast cancer.

Sally:

Okay. And are any of the researchers that were involved in this that were from Manchester?

Gareth:

Yes. So, in fact, a lot of these trials were led from Manchester. The IBIS one trial was led by Professor Tony Howell as the lead clinician for the whole study, as was the IBIS two trial, which led the Anastrozole that assessed Anastrozole. So both of those trials were led from Manchester. And in fact, both myself, I was on the NICE guideline along with Sacha Howell, Tony Howells son, which came up with the final most recent guidance in 2017 recommending the use of these treatments and the important thing is you take the treatments for five years, but they actually give you protection for at least up to 20 years with Tamoxifen. So they continue to work after you've stopped taking the medications. And the really interesting thing that we haven't published yet, from our BC predict Study is that these are women who we've assessed in the last two years where we've given them their risk feedback immediately after they've had their mammogram. Once they're clear on their mammograms, about six weeks after they're given their risk and all of the women at high and moderate risk that have come forward to have a discussion, nearly 80% of the high-risk women have gone on to risk reducing medication, which is really, really an astonishing result, because typically we're only getting around 10% of women onto risk reducing medication through the family history clinics. And it may be that it's this fresh realisation of risk that prompts women to do something additional, whereas women that have been living with  the knowledge of their risk for so many years are perhaps less willing to consider risk reducing medication and in fact, women at high risk as a result of family history are much, much more likely to go down the route of risk reducing surgery, particularly if they carry a fault in BRCA one or BRCA two. About 50% of those women by about five or six years after their result, choose to have risk reducing surgery.

Sally:

So just kind of touching on the risk side of things. So your BC predicts and pro-can one and pro-can two looked into the potential of offering women this risk stratification of their risk of developing breast cancer in the next ten years. So I'm just wondering, what are some of the potential disadvantages of telling women they are both either at higher or lower risk of developing breast cancer.

Gareth:

So I guess the main potential disadvantage is I'm saying their potential because we think actually they're not such a disadvantage as our study is showing, is that women who are told they are high risk could become very anxious and have a great deal of cancer worry. And that might be actually something that is strangely a disincentive for them doing anything about it. They may feel that it's going to happen to me anyway. I just don't want to know. And the women at low risk might be falsely reassured that low risk means no risk and might detach themselves from any sort of monitoring, having any sort of mammograms. And we've found in PROCAS one, that those women actually do not detach themselves, that they're just as likely as average risk women to continue with their screening. And that has recently been published in the Breast Journal. But in PROCAS two, we've shown that there really is no significant increase in either breast cancer anxiety or risk concern in the moderate and high risk groups. And in fact, many of the women who were found to be high or moderate risk already had a perception that they might be at some increased risk of breast cancer. So their perception of risk was already higher, possibly due to family history and other risk factors that they knew about.

Sally:

Okay. I guess it's really interesting to actually look into that multidisciplinary side of the research and look at the health psychology as well as the actual science behind these diagnoses. And I guess leading on from that, I'd like to ask what your vision is for breast cancer screening by 2030. And we've heard about Sajid Javid's war on cancer. But I'm wondering personal to you what that vision would be for breast cancer screening.

Gareth:

So my vision would really be that all women are offered a risk assessment when they're 30 or around the age of 30 because breast cancer is vanishingly low before that point. And we can do a lot of the breast screening starting from 30 or at least 35. We've shown that screening is actually effective and reduces mortality in women between 35 and 39, for instance. And if we did that, we would identify about one in five women who would qualify for early screening. They would qualify potentially for taking Tamoxifen before the menopause. And we could substantially reduce the mortality from breast cancer in that group of women by that combination of taking preventive medication and early detection, and then women would be reassessed at the age of 50 when screening would normally start to assess what their screening would be going forward. From that point onwards, would it be every year if they were high risk as recommended by NICE? Would it be every two or three years or maybe even every four or five years if there were very low risk? And it might be that we would say, well, you know, your screen at 50 is fine, we will if you're low, very low risk bring you just back in in five years and reassess things. But give women the option if they feel they have developed an additional risk factor to have their risk reassessed. So, for instance, their family history change, a sister's diagnosed with breast cancer. That might affect their risk assessment, although going forward, the genetics is accounting for more and more of the inherited component. So eventually we may not even need family history to assess risk because we're assessing that already in all of the genetic testing that we're doing.

Sally:

Okay, so you've got PROCAS two that's in its review stage at the minute. What would be the next stages that you'd look at with that study to enable this progression to your vision of screening?

Gareth:

So we have a study that's in set up at the moment, which is a young women study, where we are going to offer a low dose mammogram, about a 10th of the dose of a normal mammogram to assess the breast density and to do the polygenic risk score and potentially the test for the other genes, as well as using the standard risk factor. So this would be a study that would potentially legitimise the idea of doing a much earlier screen to determine risk. And I think, you know, going forward, we would hopefully, there is other research which will be coming out from the My Pep study, which is doing actual risk stratified screening at changing the risk, changing the interval of screening to one yearly in the very high risk and the high risk staying at two yearly for the average risk and then going to four yearly for the low risk and the Wisdom study which is similar in the States and going to the national screening programme assuming that the data continue to back up this risk stratification and saying, look, we need to be doing this and going forward, that would be, I think, an initial assessment, you know, as we say, around 30 years of age and then a second assessment at around 50 years of age. So women who were already approaching 50 would get that first assessment in that 50 age group, women who were in their thirties. I think we would have to work through that population slowly to make sure that eventually we got to the situation where every woman had been offered that risk stratified approach, at least up until 60 years of age. And that we then just did those two main assessments, one at 30, one at 50, potentially one more at 60. But again, the research will tell us if that is the right way to go forward. And we would have a fully not one size fits all where we can we can offer this screening. And importantly, and I've just looked at this data, the idea that, you know, you need a family history to be high risk of all of the breast cancers we've picked up when we use all of the risk factors together, half of the women who develop breast cancer, who we classify as high risk, have no family history of breast cancer at all in either first or second degree relatives. So it's really important that women don't think they can't be at high risk because they don't have a family history. There are many other ways they can get there. The genetic factors may not have shown themselves in other people because it's a deal of the cards. It might be different in you to your previous relatives and your mammographic density may be different or your relatives just may have been lucky. So for instance, we know you can carry a fault in BRCA one or BRCA two and there be no family history. So again, no family history is not immunity from risk. It just means overall, the likelihood of your risk is to be lower than someone who does have a family history.

Sally:

Okay. Finally, to summarise, I guess we've kind of covered it, but it's to get that kind of 2 second snippet of should we screen all women for breast cancer?

Gareth:

So I guess the standard answer is, yes, we need to screen women for their risk first. So that's the screening test. I think there may come a time where we will identify women at such low risk that those women may decide themselves that it's not worth them having the screening, you know, it's a little bit uncomfortable. The chances of false positives will be so much higher than the chances of getting cancer that they just decide, nope, no, I'm not going to I'm not going to have it. Maybe they'll be a better test, like a blood test that that doesn't have the same false positivity that mammograms have. So at the moment, yes, every woman should be screened or be offered screening. We can't force women to obviously get breast screening. But the evidence suggests that risk stratified screening is much better at balancing the benefits and the dis-benefits of what screening does. And that may mean that we do less screening, that we start screening later in those women at lower levels of risk. And it may eventually mean there'll be a group of women at such low levels of risk that we just stop screening altogether for them.

Sally:

Okay, fabulous. I'd like to ask what's made you curious about breast cancer and breast cancer research?

Gareth:

So I guess sometimes it's where you end up rather than what you necessarily had in mind. So I was a paediatrician and I became very interested in genetics. I was interested in genetics at medical school, didn't realise there was an actual profession in genetics. So while I was a paediatrician, I discovered that you could be a clinical geneticist. So I then looked around for jobs. I was actually in the army at the time as a, as a paediatrician, and I went for a job interview in Manchester for a clinical research fellow, and the job of that clinical research fellow was to set up cancer genetics services in the northwest of England. So my remit was essentially to develop services for people who were at increased risk of developing cancer. So there are syndromic cancers, but by far the biggest demand was from women who were worried about their risk of breast cancer. I started this in 1990, and in that year the BRCA one gene was identified as being on chromosome 17. The TP53 gene was a cause of Leigh Fraumeni syndrome and they have the highest risk of breast cancer with TP53 gene faults up until the age of about 50. And I was really fascinated to work with women to understand how women perceived risk, how they understood risk, because I was talking to them about risk. And that's really how it all started. And I've worked on breast cancer and breast cancer risk since the 1990s, initially just on women with a breast cancer family history. But from 2009, we decided that we would look at this on a population basis, and that's how the PROCAS study was started that I put in an application to the NIHR and we got a five year programme grant which is PROCAS predicting the risk of cancer at screening. And it's that study which recruited 58,000 women that has really given us huge information. That's the study that shown us what proportion of people are moderate and or high risk and what proportion of cancers we can pick up. It's shown us what happens to the screening going forwards. It's shown us about the weight gain issue. These are all factors that have been born out of that. But really, as soon as I had the opportunity to work in the breast cancer field and to develop the services for breast cancer in the Northwest, I was hooked and I wanted to help women who have that risk going forward since 1990.

Sally:

What an answer. And I think I mean, listening to that and listening to all the work that you've done, it's a lifetime worth of work and there's a lot kind of behind it. And I guess my kind of final question would be what continues to inspire you in breast cancer research?

Gareth:

What inspires me is the women themselves that the women who come forward and want to know about their risk, what they can do about their risk, the women that go out there and raise the money, that allows me to do a lot of the research that I do. But it's also that discovery factor. It's looking at the data and saying, gosh, I've just found something that's going to be important going forward. So I'm inspired by being able to identify things that are important, identify risk factors, and identify things that we can do. The more and more we can do, the more we have in our armamentarium to try and prevent deaths from cancer. And preventing deaths from breast cancer is about prevention, but it's also about early detection. And so working with those two together, I think we can make a fantastic contribution to reducing the 11 and a half thousand deaths per year from breast cancer, especially if we can get in and do this do this assessment earlier in the early thirties, that is the stage where women are losing more life years they're dying when they have young children. We should be trying to prevent those breast cancers because that's really where the most is lost.

Sally:

Great stuff. I mean, I want to say thank you so much for speaking to me today. It's been enlightening for me and I hope for the listeners as well, and I'll link all the references that we've made in this discussion. But honestly, you, Gareth, very inspirational and it's pretty great chatting to you.

Gareth:

It's a pleasure. Thank you.

Sally:

If you've been affected by anything you've heard in this episode, please see the show next for our list of charities and organisations that can help.

Speaker 3:

One in two was brought to you by The University of Manchester and the Manchester Cancer Research Centre. Listen to our next episode to hear from more of our researchers as they share the innovations, discoveries and projects that are changing the landscape of cancer prevention, early detection and treatment. To find out more about what you've heard today, please see the show notes for this episode, where you'll find a transcript and links to further information and research. Cancer is one of the university's five research beacons, showcasing the interdisciplinary collaborations and cross-sector partnerships that are tackling some of the biggest questions facing the planet. To hear more about Manchester's research in advanced materials, biotechnology, cancer, energy and global inequalities go to Manchester.ac.uk/beacons.

 

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Professor Gareth Evans  

Gareth Evans is a Professor of Medical Genetics and Cancer Epidemiology at The University of Manchester. He is also a Consultant in Medical Genetics and Cancer Epidemiology at Central Manchester Hospitals NHS Foundation Trust and The Christie NHS Foundation Trust.