Professor Michael Baum is confident that one day a rational, biological treatment for breast cancer will be found. It may be 10 or 15 years away. “”But in the meantime we cannot do nothing,” he says. So he is doing something, but he has come under a lot of irrational resistance.
Baum is on the co-ordinating committee on cancer research and is a professor in the department of surgery at University College Hospital in London.
He is working on a clinical trial of the drug Tamoxifen. And is seeking volunteers. It is different from a lot of medical trials. Rather than seeking people with disease and giving a new treatment to one group and no treatment or conventional treatment to another, this trial is not for people who have been diagnosed with cancer, but rather their sisters, daughters and others in families with high risk factors. The idea is that if the volunteers take Tamoxifen over five or more years it may prevent the onset of cancer. But Tamoxifen can cause cancer of the endometrium (the lining of the uterus).
Meanwhile, a colleague and friend in Newcastle, Professor John Forbes, is conducting the same trial. So are some colleagues in North America. The incidence of breast cancer is similar in Australia, Britain and North America, but the advantage of the triple trial is greater statistical certainty. He says of his work with Forbes: “”It is truly a remarkable collaboration.”
For nearly two decades Tamoxifen has been prescribed for many women with breast cancer. The drug interferes with the receptors on cancer cells that enable the cells to feed off oestrogen. Its full biochemical effects are not fully understood because it sometimes works with post-menopausal women who are not producing oestrogen. Like most of the drugs used to combat breast and prostate cancer its effectiveness lies in changing the hormonal balance of the body in a way that cancer cells do not like, but with which the body can generally cope, causing few serious side effects.
Other than hormone treatments, the only other treatments for cancer are surgery (cut it out); radiation (zap it); and chemotheraphy (poison it). Each of these, of course, have unpleasant side effects, particularly chemotheraphy. The poisons that kill cancer cells at present are not specific enough … they also attack a large range of other normal cells that, like cancer cells are generally fast growing. These are mainly the hair and the digestive tract, particularly from the mouth to the stomach. None the less these three treatments are the basic armoury in the present state of medicine.
At lot of present research is geared at making these three more effective or equally effective with fewer side effects. Baum is looking further afield: to prevention (with Forbes and other colleagues) and to other methods of biological control without nasty side effects.
The present popular perception of breast cancer treatment is largely one of inaccurate extremes. The popular fear is one of diagnosed today, dead tomorrow. The popular journalism tells stories of “”How I had a mammogram, had it caught early, removed and lived happily ever after or with love and care adapted to life with one breast and lived happily ever after.”
The truth, as is often the case, is less dramatically in the middle … long-term management of a disease which flares from time to time in places in the body, each life-threatening, but often, though not always, treatable.
Baum wants to find better ways of long-term management away from the big three … surgery, radiation and chemotheraphy. More of that anon. At the other end of the scale he is looking at prevention.
Baum and Forbes think it possible that Tamoxifen may prevent or reduce the risk of breast cancer in high-risk groups. But there a couple of snags which illustrate the difficulty of modern medicine.
A lot of earlier medical scientific advance had demonstrable and certain results, for example, Pasteur’s penicillin, Jenner’s smallpox vaccine and Salk’s polio vaccine.
The easier ones have been done. Modern medicine’s difficulty is dealing with things like cancer, diabetes, multiple sclerosis and AIDS where there are no biochemical certainties. Most of the treatments can only be couched in terms of likelihoods and probabilities of reductions in death rates.
And when you deal with probabilities and statistical risks, you run into two big snags … opposition from the unscientific and who will pay. I spoke to Baum in his London office, beneath one of his abstract paintings. After the interview he was off to painting class.
“”There is an enormous ethical issue here,” he said. “”The lay public wants us to cure cancer and prevent cancer as long as it is not in people. You want us to do it in rats and then do it on human beings afterwards. So you have got this extraordinary ambivalence of the lay public. Yes, they want us to cure cancer, but they want it to be natural and they don’t want it to be experimental. We have a serious clash of culture between the clinical scientists who say, “yes we have within our grasp ways of preventing cancer and improving treatment of cancer, but in order to demonstrate that this is true we have to do a clinical trial.’
“”Then it becomes an ethical issue because the patients say I want the best treatment. I don’t want the placebo. I don’t want an experiment. But the doctors don’t know the best treatment otherwise there would not be a trial.
“”And so there is this terrible tension. The only way to resolve it is to involve the lay public so that they have a proprietary interest in the trial.”
Baum said he was just getting to that stage now. Rather than scientists wanting to do the trial on women, women were wanting the trial to be done on them. But there had been a shrill opposition.
“”There are two agendas here,” he says. “”There is one that you are giving a dangerous drug. Disease substitution is the cliche they use. Substitution cancer of the endometrium for cancer of the breast.
“”The other shrill voice is the feminist lobby that bitterly resents men having power over women’s bodies. And that goes hand in hand with a naive view that nature is best that it is not natural to give drugs that you can do it naturally with diet and exercise.
“”No-one pretends that all intervention by mankind is all good will do no harm. What we say that you do a clinical trial to work out the harm is and the benefit is. “”We do clinical trials to work out whether the gain can more than compensate for the pain. We make estimates. And the estimates are overwhelmingly in favour of the trial.”
The latest unpublished data suggests that taking Tamoxifen would reduce the risk of breast cancer by 50 per cent.
Dr Baum says, “”We know this from the trials of women who have already had breast cancer. If a women has had one breast cancer she has a one per cent chance of each year of getting an entirely new cancer on the other side. That risk is halved by five years of Tamoxifen. We have the potential to halve the risk of breast cancer among high risk women.
“”Tamoxifen also reduces cholesterol and reduces the risk of heart disease, but the harm is the increase in endometrial cancer. The risk is increased three fold … from three per 10,000 per year to 9 per 10,000 per year.
And then Professor Baum moves from quiet explanation to the passionate scientist concerned about his work and womankind. “”It is tiny risk,” he says. “”And three times a tiny risk is still a tiny risk. I get so cross by these constant alerts and alarms.”
Baum estimates the for every six extra endometrial cancers Tamoxifen would prevent 50 breast cancer cases. And as 90 per cent of endometrial cancers are curable, but about half of breast cancer patients die from their disease, it is worth doing the trial to see if Tamoxifen also works with women who have not been diagnosed. “”You are trading off one death for 25,” he says.
However, the difficulty for Baum is you can never point to the women who benefit, but you can always point to the women who can say, Your Tamoxifen caused my endometrial cancer.
The British trial went through an exhaustive ethical review, far longer and harder than the Australian one. The trial became a hot one in Britain when it was denounced by feminist Carolyn Faulder on the very popular Woman’s Hour radio program. Baum says the review seemed like a Star Chamber.
“”We were cross-examined with sweat pouring off our face. Theologians, philosophers, ethicists and lawyers looked at it and finally approved it.
“”There has been a lot of aggravation. Many’s a time when I’ve we have felt like chucking our hand.” What keeps him going then?
“”I think it’s my belief in the scientific method. I’m passionate about science and humanity,” he says. “”I care very deeply about women’s health matters.
“”They try to portray us as misogynist. I’ve got daughters I worry about I’ve got a wife of 30 years. I want to contribute to women’s health, and I want to defend the scientific process.
“”If this trial is aborted it means yet another triumph of the anti-science lobby. And there is a lot of it out there. So I am personally making a stand for womankind for science against the ill-informed.” But there is a counter-point, here.
Baum says of all the trials he has had to recruit for, this was the easiest. “”First, the woman does not have cancer so she has got time to think it through, she is not in a panic,” he says. “”Secondly we say to them they are not doing it for themselves, there are volunteering for the sake of their sisters and daughters. And when you put it to a woman from a bad-risk family to join this trial that by the time your daughters are old enough to get breast cancer we may be in a position to prevent it. A woman’s natural reaction is I will sacrifice my life, if necessary, for the sake of my children. It just appeals to the natural altruism of women. “”So it’s a damn shame those women are being inhibited.”
Baum is aiming for 20,000 volunteers, but expects about 16,000. He expects the Australian side of the research will get more than 5000 volunteers. Baum clearly gets moral support from the international scientific co-operation. He has taken on his detractors with determination and courage, even if he is utterly perplexed by them.
“”In the end it is malicious,” he says. “”In the end I don’t understand the motives. We have nothing to gain personally. I am already a professor. I can’t be a professor professor.”
There is a further hurdle to helping women fight breast cancer. If the trial does indeed show that Tamoxifen reduces risk, then governments have to be convinced to supply Tamoxifen to high-risk women when there is no presence of disease.
“”Then its over to the health economists,” Baum says. “”They wanted to hold up study to build in health economics. It held up the trial for a year, and then we discovered that the very models the health economists were using are very weak compared to the simple questions were asking.
“”How do you make a health economic argument? You have to weigh up the cost of providing Tamoxifen against the cost of treating people with breast cancer and caring for families who have lost their mothers. It is a very complex argument.
“”So we said let’s push ahead and demonstrate if there is an effect and then it is up to the health economists to work out cost effectiveness. “”What they are worried about is that it will be an embarrassment if we show a risk reduction and there will be a clamour for people to have it. This is going on all the time.”
Baum is worried that medicine gets too politicised. This had happened with mass screening for breast cancer, he said. “”I happen to think screening for breast cancer is very poor value for money. Given the same amount of money we could save more lives from cancer if we had the money used on screening.
“”But that is a politically sensitive thing. Screening was introduced before there was a proper health economic evaluation. And the estimates for saving a life from screening are all over the place … from 30,000 pounds to a million. “”Tamoxifen is only one example of tough decisions they are going to have to make if they want evidence-based medicine.”
He said there was a 5 per cent less chance of a woman dying from breast cancer in Britain if she went to a super-specialist clinic. But there was not the money to treat all women that way. If the screening money were spent on super-specialist clinics it would produce as good or better result than mass screening without bothering the well women.
“”More money should go for research and new treatment,” he says. “”We have many promising new treatments but very little money for trials. There is only finite money for health care, and the apportionment between the diseases is a political decision, which I accept. But that money should be spent in the way that saves the most lives.”
Britain was fortunate in having the Co-ordinating Committee on Cancer Research to help do that, but screening had been fenced off because it was so politically sensitive. What about screening for prostate cancer in men. “”It’s the same with knobs on, if you’ll forgive the expression.
You should not screen. I won’t let my doctor do it to me. It will be over diagnosed in about 80 per cent of cases.” That would cause a lot of unnecessary and harmful treatment.
“”Medicine is divided,” he said. “”Those who believe in screening and those like me who thing this is a fascist, coercive approach to treating human disease. I just don’t like going out there trawling for disease amongst well people.”
As to new treatments, Baum said, “”Most of the excitement is at the molecular level: defining the oncogene determining the genetic pre-disposition. Ultimately rational biological therapies will emerge in 10 to 15 years.”
Baum foresees biological and molecular treatments paralleling the approach with the treatment of diabetes. Diabetes used to kill, now is controlled not cured, but patients live a long time.
Most present treatments aim at killing every cancer cell in the body. He would like to see some research in a different direction. One that accepts there are spots of cancer cells in the body (often very small, undetectable by present imaging, and presenting no immediate attack on vital organs), and that treatments could be found to keep these spots in what he calls dynamic equilibrium, preventing them from growing to a threatening size.
He describes these cancer spots as being on the edge of chaos, so that at any stage they might grow more quickly. He would like to see more research that accepts the spots are there but ensuring they stay under control in dynamic equilibrium. Research into how cancer cells synthesise proteins and how they get a blood supply would help.
This would be better than present attempts to kill every cancer cell through chemotheraphy, because the poisons in chemotheraphy might also be killing patients or at least reducing their capacity to keep the disease at bay naturally.
One of the more recent treatments, for example, involves giving very high doses of poisons, so high that all the bone marrow is killed, too. The bone marrow is replaced by re-injecting bone-marrow stem cells that had been rescued before the poisons were introduced.
The theory with chemotheraphy is that the poisons are more poisonous to cancer cells than to body cells, killing all of the former off, but allowing the body cells to regrow after the treatment.
Baum hopes to find a better way. “”I think we have plateaued with present treatments,” he says. “”We need a new approach to research.” Crispin Hull visited Britain as a guest of the British Foreign and Commonwealth Office.