Highlighting Welsh Cancer Research

Breast cancer in Wales - a success story

Prof Peter Barrett-Lee - Cardiff University, Cardiff, UK

This is breast cancer in Wales – a success story, or what has Wales done for breast cancer, OK? Basically first of all I’ll say, well what has Wales done for me? It’s been a fantastic place, I tell anybody who asks me it’s the best move I ever made, to come from southern England to Wales 22 years ago. Since that time we’ve built the beautiful Cardiff Bay, I’ve been up Kilimanjaro and got to the summit at 20,000 feet with one or two famous people and I would never have done that. I’ve met the Manic Street Preachers, I even count some of them as my friends. I’ve become Medical Director in Wales and we’ve seen screening introduced here and breast cancer survival has improved dramatically. So it’s all been great for me, so thank you Wales for that.

In terms of some really serendipitous things that happened, when I came down to Wales Malcolm was here so that makes life a lot easier. He’s a wonderful chap and a great colleague and supporter. These two people, in the middle Professor Nicholson, Rob Nicholson, and on the right Julia Gee, who is still my friend and colleague, Rob retired recently, they were funded by the wonderful Tenovus and were doing fantastic breast cancer basic research into endocrine resistance. That put us in position when John Yarnold came up with his ABC trial which was the first large-scale UK trial in breast cancer in Britain with over a hundred centres, he brought them together, until then everybody did their own thing in small studies. We were able to nab the biological studies because Malcolm was here and we had the expertise. So thanks to Tenovus and these people we were able to nab the biological studies for the ABC trial. That’s just showing you it was a truly international trial; if anything, actually, we’ve gone backwards because of EU directives and things since then such that it’s got a bit harder to do international trials than it was. But there we are, it’s a work in progress. I won’t go into detail, suffice to say this was a very important randomised trial. Patients if they were premenopausal were randomised to either chemotherapy or no chemotherapy or ovarian suppression or no ovarian suppression and just in the post-menopausal patients they were randomised obviously not to ovarian suppression, because they’ve already had that naturally, but either chemotherapy or no chemotherapy. The important thing was although we showed that chemotherapy benefitted this predominantly older age group, all that data on the left has gone into the Oxford overview and gives it more power to detect the benefits of chemotherapy in the older patient group. On the right is showing that ovarian suppression made no difference. Now, more recently we’ve discovered through other trials that very young patients, in their 20s and 30s, may benefit from adjuvant ovarian suppression but that’s quite a tough thing for them. But in this predominantly over-40s group who were premenopausal chemotherapy plus ovarian suppression did not do any better than chemotherapy alone. So ovarian suppression we showed not necessary.

We were also, as I said, able to nab the biological studies and one of the outcomes of this is this really important observation which isn’t our own only, others have seen this. But because we’ve got fifteen years’ follow-up in the ABC trial what you see there is the numbers of patients at risk along the bottom over time and up the side is the relapse rate by oestrogen receptor status. Something that a lot of us instinctively knew but has been hammered home time and time again recently is that oestrogen receptor positive disease, which curiously here is shown in the blue, is a continuous relapse rate for fifteen years. So it seems to be a good prognosis type breast cancer, and it is in a way, but it has a constant relapse rate. Prostate cancer may want to learn from that. If you look at the ER negative disease in the red, it has a very early relapse rate and then slows right down and you could argue at fifteen years those patients have a flat curve so they’re probably cured whereas in ER positive disease you’re never cured. That’s something now that has led to the advent of ten years of adjuvant therapy with endocrine treatment.

OK, so let’s go back a little bit. No-one here, apart from Gordon, may know that on the left is Professor Walpole who discovered or kind of discovered the whole area of tamoxifen and anti-oestrogens. On the right at the top is Craig Jordan who has become a very famous American endo-biologist but in fact is British originally and on the left a bit lower down there is Mike Baum, a very young Mike Baum, who I’m sure Gordon had many associations with, and on the right is Helen Stewart who was now by then in the Scottish cancer trials. The particular of that trial, that slide, is that in the ‘70s there was a meeting at Kings College, about ’77, and these three people got together and came up with the ideas for the longer adjuvant tamoxifen trials, so one or two years of tamoxifen versus not. What’s really important is that we gave the rest of the world Mike Baum because he, at that time just before Kings, was working in the Cardiff Breast Unit. That’s the quote from Terry Priestman who was a clinical oncologist working in the clinic that I now work in saying that ‘Working with Mike Baum was totally harmonious, I always did what he told me,’ and how Baum had described to a patient that they were the Starsky and Hutch of breast cancer, which fascinating. It also tells you what the era was, doesn’t it? So I walked in after these guys and, interestingly, you will see they actually were very innovative. So this is the Cardiff Breast Clinic in the ‘70s already coming up with a randomised trial. And that’s actually still a question today of endocrine therapy versus cytotoxics. At the bottom there you’ll see the names and all of those people appeared in patients’ notes when I took over. There were still patients who had been treated by all of those. So Cardiff actually probably one of the first truly multidisciplinary breast clinics and had such leaders as Mike Baum. Moving on, there we are, so Mike eventually went on, as you know, to take a lot of credit for adjuvant tamoxifen but it wasn’t just his story, it was many others as well.

So, what else have Wales done? Actually, on the left there is Pat Forrest who again was a Cardiff Breast Clinic person, quite a bit before Mike Baum, different era. Pat Forrest then moved to Edinburgh but he wrote the Forrest Report which recommended screening to the UK. That’s Ian Moneypenny there who, together with Bob Mansel, Helen Sweet  and others, set up the Breast Test Wales i.e. the breast screening programme in Wales. I can honestly say I think it’s the highest quality screening programme that I’ve ever seen. I am biased because I work within it but they’ve never had a major investigation or a major scandal, the pathology is tip-top and they publish their results and they are outstanding. It’s one of the best things that Wales has done for breast cancer. So I take my hat off to them.

Again, the next thing here, this is major work. So Professor Bob Mansel who I was actually at his retirement little do last week, although he’s not going to really retire either. So what did we do for the world? Well, we brought sentinel node biopsy to the mainstream. Yes, it was started in the States but they never did a randomised trial. We did the randomised trials, or rather Bob set up, did it with all the centres in the UK, introduced sentinel node biopsy, got the evidence that it is cost effective, no-one had done that, and that it has lower morbidity than the standard axillary dissection. But, more importantly, we made sure that all the surgeons in the UK were trained to do it properly; there is a learning curve. If you just go in and start doing it we can show that it doesn’t work and therefore you’re telling patients they’re node negative when they’re not. So that is a major piece of work and Bob has won many accolades for that. So we gave that to the world.

Just so that you think Swansea is left out, it’s not. This is Professor Bob Leonard who during his time when he was a professor in the Oncology Centre in Swansea was co-ordinating this Anglo-Celtic high dose chemotherapy trial. Now, you might think what’s all that about, it’s all old hat now. In the ‘90s it was the best thing since sliced bread. People were mortgaging their houses to pay the thirty grand to have a high dose chemotherapy treatment and stem cell transplant for breast cancer because the Americans had a non-randomised trial showing that it just improved your survival by a huge amount. We did the trial – no difference. This is a huge undertaking in pre-NCRI days, 600-700 patients randomised to a very expensive high dose chemotherapy treatment but it was no better than standard therapy. So again you could argue the Brits are very good at doing negative trials but there was a lot of harm being done around the world with high dose chemotherapy. It had no basis and we stopped that.

OK. Those of you who know about HER2 positive breast cancer will know that’s Dennis Slamon, wrapping up, yes. That’s Dennis Slamon, he was very much part of the development of trastuzumab. The small part we played in all of this is that we were involved in the pivotal trial, us and Bob Leonard actually who had now gone to Edinburgh, and we managed to beat him to put the first patient in Europe into the Herceptin trial. So, first patient in the UK received Herceptin in Wales. Of course you know it went on to be an established treatment and then the adjuvant therapy has just changed the world. Just an important thing now, on the top right is what Herceptin has done is if you’ve got HER2 positive disease your survival is now as good as if you had HER2 negative disease. So it has completely cancelled out the poor prognosis of HER2 positive disease.

I just can’t not mention the Wales Cancer Bank. We’ve given the world one of the best cancer banks – well documented, run rigorously with great governance and control procedures and it’s going to go on to new and greater things, concentrating particularly on the big areas of unmet need and providing our researchers with the tools that they need. The UK TACT trial, I was involved in this. We gave the world a trial which actually, with my colleagues there, Judith Bliss and Paul Ellis, showed again it was a negative trial. We showed that taxanes don’t do anything in the adjuvant setting, particularly for oestrogen receptor positive breast cancer patients.

So, again this started the Wales Cancer Research Network and WCTU. This was a trial that I again conceived in Wales, run by the WCTU for the whole of Wales, comparing zoledronate with ibandronate. We actually showed ibandronate was inferior, a lot of centres were using ibandronate so after this was published I rang them up and said, ‘Do you realise you’re using an inferior treatment?’ and they were quite shocked.

We’ve also, I think, charities. This is the In the Pink ladies who have supported a lot of breast cancer research as of Tenovus. One of our strengths in Wales is we have done a huge amount of charity work and we have some fantastic charities and I thank them all. I won’t do the basic science but this is what they’ve supported; one of our observations has led to this trial. I was contacted by David Cameron, I’m the co-Chief Investigator on the Src inhibitor trial, we’re about to analyse the results so we may have actually produced a new treatment.

Just to say, we also have Cardiff researchers producing a new BCL3 inhibitor for trials in phase I. Jaz Abraham over here, winning awards for setting up a metastatic breast cancer clinic, an MDT, which is again the first in the UK, we’ve won awards for that. We’re undergoing a massive transformation of South-East Wales breast cancer and cancer services in general and building a new cancer centre in the next five years.

So those you can read the conclusions in the future. I think we’ve had a fantastic success story in Wales but no resting on our laurels, we need to go forward. Thank you very much.