Future direction for breast cancer treatment

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Published: 20 Jul 2012
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Prof Michael Baum - University College London, UK

Prof Michael Baum talks to ecancer.tv about the need for a dramatic change in the way breast cancer treatment is approached.

 

In contrast to the popular view that personalised therapies are the future of breast cancer treatment, Prof Baum argues that the cost of this approach is not outweighed by the potential benefit.

 

Prof Baum suggests how research resources could better be used especially considering the high proportion of the global cancer burden that is found in less developed countries.

Professor Michael Baum, you’re here talking about a personal perspective on breast cancer. Can you tell me what was your motivation for getting really into breast cancer in the first place?

Well the personal perspective is twofold: one, my family, literally my personal involvement at a family level, and the other my history of involvement in research and treatment of breast cancer over forty years. My family has a bad history of breast cancer; my mother died in agony with neglected breast cancer about forty years ago so that kind of galvanised me. It made me angry, and nothing like anger fuels your passion for work. Then about twenty years after that my young sister developed breast cancer but she survived and she survived as a result of the revolution in treatment between my mother’s diagnosis, which was too late in any case, she had advanced disease with skeletal metastases, and my young sister who presented with a small clinical breast cancer. She had the benefit of lumpectomy, breast conserving surgery, radiotherapy and that was nineteen years ago, she’s done very well. But then my family is Ashkenazi and I think an aunt probably had breast cancer and I think my maternal grandmother may have had it but they didn’t talk about it. So being Ashkenazi and with two first degree relatives with breast cancer it was decided that my sister should be tested for the Ashkenazi mutations and she tested negative. But nevertheless it’s in the family and there are seventeen young women in the next one and two generations who are at risk of breast cancer. So it is my quest not for womankind in general but for family.

Now I know that you have been passionate about breast cancer and in particular passionate about not just doing things because it’s the fashion to do them.

Yes, I’m a thorn in the flesh of people who accept the received wisdom. I have a default position, when everybody agrees, ‘That’s it, we’ve got it,’ I dissent. Because the process of advancing in science is dissent and there are lots of things; we’re doing pretty good but I think we’ve plateaued. I think it’s time for revolutionary concepts actually.

And, for instance, we’ve left behind over-aggressive surgery in breast cancer, haven’t we?

Yes, the conceptual revolution in the early 1970s, led by Bernie Fisher and he mentored me, was the disease was systemic at the time of diagnosis. That led to breast conserving surgery and adjuvant systemic therapy and that has served us very well until now. We’ve kind of plateaued, every advance is a tiny increment. But along the way no-one has spotted the outlying observations which mean that that is not the complete truth, other things are happening.

But a big hope was injected by hormone dependency and the fact that a particular part of the molecule could be a key to living a lot longer.

That was a real breakthrough, tamoxifen and the oestrogen receptor, that’s a real breakthrough. People are talking about personalised medicine, we’ve got to have personalised medicine, that’s the next big thing. It’s not the next big thing, it’s yesterday’s thing. Tamoxifen was the big breakthrough for personalised medicine; 70% of women express the oestrogen receptor and benefit from the endocrine therapies. That’s personalised medicine.

Now I want to ask you about personalised medicine and some of the molecular ideas but let me digress and ask you about mammography and screening because that is still an open question, we’re beginning to hear at this meeting, or is it?

Yes. Breast screening by mammography has a great future behind it. I speak as someone with a family history of breast cancer, I speak as one of the architects of the programme, I was given the task after the Forrest Report to set it up in the south-east of England. I have every reason to want it to be successful. I think it is an absolute disaster. We’ve reached the point where I have little doubt the harm outweighs the benefits and we should stop it.

But at the moment we’re hearing a huge amount of talk about individualising therapy through molecular species and looking at the molecular nature. There’s a lot of hope based on this, isn’t there, at the moment?

Yes, I think it’s false hope and I think it’s utterly unrealistic. One of the things I’ve heard at this meeting, again which makes me passionate and angry, is how the poor women in the developing world, the under-resourced world, are suffering with horrible advanced cancer with none of the benefits that we’re seeing in the rich parts of the world. It infuriates me to learn that 50% of all the resources in the world in the treatment of cancer is in America and only 5% of the burden is in America. That is just distributive justice gone mad. The kind of personalised medicine where you get the molecular profile of every cancer and then you do a clinical trial of treatment for that individualised cancer which is split up into, say, twenty subgroups is utterly unrealistic and unaffordable.

But could it be productive in some cases?

It might well be but it’s unaffordable, it’s unrealistic. What I think is we need another oestrogen receptor, Tamoxifen, a big leap forward and I think we’ll only get that by looking at the system, not the molecule. I think we’re obsessed with the molecule, I don’t think that’s the answer. I think we have to understand what is happening in these micro-organelles that cancer metastasis isn’t a cluster of cells, it’s an organelle with its vasculature and cells in dynamic equilibrium. That’s what we should focus, not the molecular structure, the cell, but the whole organelle. My group of mathematicians, biologists, clinical triallists, have been shortlisted for one of the Impact grants at the Department of Defense. We’ve been shortlisted, I think 5 out of 250. They think that we’re in with a chance, it means we’re saying something sensible.

Now, it has been shown that breast cancer survival has improved; a good part of that may well be because of tamoxifen and hormonal therapies. But what do you think needs to be done to individualise it in the correct way then?

First of all we shouldn’t talk about survival, we should talk about mortality. Breast cancer survival increases phenomenally when you screen. You’re over-diagnosing, all these cancers are never going to kill you in any case so you get fantastic survival. It really angers me, people who ought to know better talk about survival in the population where they’re over-diagnosed. If we look at mortality we are doing well but we’ve plateaued and we need another kind.

Mortality improvements have been due to what?

Systemic therapies. Not screening, and the reason I know that, in the United Kingdom there has been a precipitous fall in mortality from breast cancer, it started ten years before screening was introduced and it’s at its maximum in the under-50s which are not screened. So it is obscene for the screeners to claim credit for the fall in mortality. So systemic therapy has done wonders. We have plateaued, we’re now getting tiny incremental improvements, we need the next big leap.

What is the next big leap? Where would you put your priorities?

On a conceptual revolution and the revolution is centred on mathematics. We’ve got the mathematics wrong. All the ideas about the growth of breast cancer and the kinetics of systemic therapy are based on the linear or log-linear model. It worked a little but it’s not right. The only way you can explain breast cancer is by using chaos therapy. Working with mathematicians around the globe we’ve published thirty or forty papers which explain. They say breast cancer is unpredictable, well it’s only unpredictable using the wrong maths. It’s like the weather, once you use chaos theory maths for the weather you can predict it within the next week or two. You can then start predicting breast cancer if you use the right maths. We’ve got the right maths and we’ve published it and it certainly has interested the Department of Defense in America.

So what should ordinary people do, cancer clinicians, how should they view these developments or these plans that you have?

Well what I ended my lecture, I said the future is rosy but the biggest impediment to progress is not money, it’s not resources, it’s closed minds. If people are not prepared to look outside the box, if they’re not prepared to concede that screening leads to over-diagnosis, that will obstruct progress. Closed minds. And some wise man said, these people have skulls that open outwards, the more information you give the tighter the skull closes. So we want people whose skull opens outwards and are prepared to accept and consider revolutionary new ideas that attempt to refute their belief system.

And you said, of course, the big burden of breast cancer may well be in places like Africa and the big opportunities for getting it treated may be in Europe or America, but isn’t that something that’s going to be perennially difficult to tackle?

There’s such as thing called distributive justice. I’ve just come back from Bangkok where I was asked to talk about the quality of life in the age of globalisation. I started my talk with the quotation from Leviticus: Love thy neighbour as thyself. If you love yourself what do you wish for? Health. Who is your neighbour? We live in a global world, all races and societies are our neighbour, we should love them as we love ourselves. To me, again, it is an obscenity how much over-investigation, over-diagnosis, overtreatment they have in the United States of America which is exhausting all these resources, ignoring the poor people in the resource part to the world. That, I think, is shameful. For all of that it isn’t as if the results are any better in America. Their survival is fantastic, yes, that’s because of all the over-diagnosis, that’s why they get good survival. But the mortality is not as good as in Europe.

And not only America, of course, other countries are indulging.

Yes. That’s what makes me very cross. But then Peter, as you know, I’ve always been a passionate man.

Well, I’m sure you’ll stay cross for a long time but it’s a very constructive kind of being cross. Michael, thank you very much for popping in to ecancer.tv.

Oh, it’s a pleasure. Lovely seeing you again.