This interview is with Professor Tony Howell, for CANCERactive and was originally published in May-June 2004 icon
Tony Howell talks to Madeledine Kingsley about Cancer prevention
It’s eight am, and Tony Howell the UK’s first Professor of Cancer Prevention, has already spent two hours in his office at the Christie Hospital, Manchester, poring over a scientific paper on tumour-educated macrophages. As the author of 360 papers of his own, Tony says he reads such literature for pleasure, which is just as well for one on the editorial board of The Breast, Endocrine Related Cancer, and Women and Cancer. As relaxation, he cites flying off to speak in various parts of the world. Switzerland, Bermuda, Australia and Brussels have recently figured in his diary: "Lecturing is important and the travel is almost a hobby, though I’ve never quite said so before.
Does it sound boring?" Absolutely not, nor does one for a moment swallow his joke that "there’s no human here behind the scientist". Rumbled, Tony Howell tells that he got married again last July "to a lovely lady in clinical trials". He runs to keep fit and has two children, who are also doctors.
Tony is 61, soft-spoken, lithe as a latt and fortified by the bag of fruit he’s brought in from home - a healthful five-a-day rap on the knuckles for those of us who have wolfed a Kit-Kat for early breakfast on the hoof. "Oh, occasionally I have a Kit Kat too" owns Tony with a twinkle, "and then I feel guilty, just as you do!" Modest about his awe-inspiring umbrella title, he explains that, despite focusing mainly on breast cancer, his Professorship in Medical Oncology also carries a much-needed, wider remit. "The National Cancer Research Institute do have their own prevention programme, though I understand that at present only two per cent of all research money is spent on prevention. I’m sure that will change...it must."
For women everywhere there is certainly increasing awareness of breast health, but if there’s also more fear of disease, it’s hardly surprising. Breast cancer seems almost a modern plague, as over the past 20 years, Tony reminds, UK cases have swelled from 25,000 to 40,000 a year. "Thankfully deaths are going down, but the rising incidence is a real problem. It’s related to increased hormone exposure, from the oral contraceptive, from earlier menarche, later menopause and women having later, fewer pregnancies and spells of breastfeeding."
Breast cancer seems almost a modern
plague
We are now off and away, engrossed in a free-ranging exchange about the status quo of diagnosis, cure and treatment. Some 20 years ago Tony shifted his research focus from advanced breast cancer to early breast cancer "because I think that any doctor is here to eliminate disease. You can, of course, do a lot of good for women whose cancer has recurred metastatically. You can help them pyschologically; you can cause regression of the tumour for a period of time with various treatments, but ultimately you can’t cure them. This led me to focus on the frontline treatment of breast cancer at the time of tumour removal, because with hormone therapy (tamoxifen and anastrozole) or chemotherapy after surgery we can now cure women with microscopic spread Is that cure rate increasing? "Gradually, yes," says Tony, "when I first came, we hardly gave any treatment after surgery, so nobody was being cured. At the same stage now, we can cure 25 per cent per cent of women."
But what about the possibility that surgery itself can promote spread...? "It’s a tricky one, that" says Tony, "and controversial. Some people at Guys have demonstrated that if you operate on pre-menopausal women in the first half of their cycle, they do well, whereas the second half of the cycle is a bad time. So they now only operate during the first half of the cycle. I haven’t, myself, been totally convinced by the argument that the hormonal environment probably allows more spread of cells in the second half of the cycle." And is there any clear indication which women make up the quarter of those who can be cured? "Only to a certain extent" says Tony, "We know that women with hormone receptor negative tumours can be helped with chemotherapy. As far as tamoxifen and anastrozole are concerned, only women who are hormone receptor positive can be helped. But at the moment we can’t pinpoint exactly who within that group will benefit. We have research teams looking at the genetics and the proteins of these tumours. We are also in touch with the Amsterdam Cancer Institute, who are at the head of the field using gene arraying technology to predict more precisely the appropriate treatment for individual women. I think it will still be another five to 10 years before we can pinpoint exactly which treatment to give whom."
Warmth and openness should be bottled and dispensed to med students the world over
Here is a consultant any woman in medical distress would want by her side: Tony’s learned warmth and openness should be bottled and dispensed to med students the world over. It should be liberally poured over all clinicians with the bedside manner of a cold steel speculum. So although his presence at the Christie is great for women of the north-west, it’s perhaps a shame for the rest of us that this specialist breast cancer clinic is open only to 500 local women - those at moderate risk who live in Manchester, and high-risk women from surrounding Cheshire as well as the city itself. The whole concept of high-risk clinics originated at the Christie; there are now about 17 and NICE is recommending more for the UK along the same lines. High risk women must be seen by genetic experts; those at moderate risk go to breast clinics around the network.
At the Christie, Tony Howell is one of a triumvirate of internationally renowned warriors against breast cancer. His colleagues, Prof Gareth Evans (who specialises in cancer genetics and chairs the NICE Familial Breast Cancer Guideline Development and Group) and Prof Nigel Bundred (whose field is pre-cancer breast tissue changes) comprise a formidable unit, for whom the Manchester-based Genesis Appeal is currently fund-raising lOm to build Europe’s first Breast Cancer Prevention Centre. Watch this place, with its high-profile patrons such as Amanda Holden and Joan Collins, Kevin Keegan and Bruce Jones (alias Les Battersby of Coronation Street). For it’s here that researchers are bent on a coherent programme to unravel the faulty genes that can cause breast cancer, the diet and lifestyle changes that may influence the development of breast cancer, the drugs that can prevent it and the best screening methods for early detection. It says much about this unit’s inspiration of excellence that Tony Howell’s doctor son Sacha has followed parental footsteps into the same field and the self-same hospital.
High-Risk Removal
At the top of the Urgent list for preventative care, says Tony, must be those women who have three first-line family members (mother, sisters) with breast cancer, giving them a one-in-four - or greater - risk of developing the disease. At the Christie all women in this category are offered prophylactic mastectomy which some 10-15 per cent take up. If you haven’t encountered this risk-reducing option before, it may sound drastic, even shocking. But as Tony Howell gently points out, it’s proving more successful than following the alternative regime of annual mammograms. Tony describes the emotional response of women who do go ahead with breast removal as "extraordinary. There is uniform relief at the risk reduction. Quality of life is really improved as the burden of anxiety is lifted. So is the burden of getting the disease with all the attendant treatment. If you carry the genetic mutation BRAC1 or BRAC2, then your risk is 70 per cent. Prophylactic surgery can reduce that by 90 per cent or more." This is particularly significant for women with mutations on the BRAC1 gene, whose cancers tend to be quite aggressive.
In a way, the younger they have surgery, the better
A double mastectomy, even when elective, is obviously a daunting procedure, and all Christie patients are cared for according to a strict protocol "They would see geneticist Gareth Evans twice. They would also see our psychologist and have very careful follow up afterwards. They would also be offered breast reconstruction, either with breast expanders or tissue from the tummy or the back." These women can go on to have babies afterwards, but most are in the 35-40 age range, so have usually finished childbearing. "In a way" says Tony, "the younger they have surgery, the better, because they receive more protection. Someone of 60 would have only 20 years of protection, but a woman of 35 get 55 years." The proof of the pudding is in the lifesaving: 10 years after this prophylactic procedure began at the Christie, 150 women have had the surgery, and not one of them has got cancer.
Trial By Tamoxiten
The quintessential scientist, Tony Howell stresses he won’t recommend any remedy that’s not backed up by randomised trials, If excessive hormone levels cause breast cancer, then might it not be possible suppress the levels medically? "Absolutely," says Tony Howell. "So much breast cancer is caused by oestrogen. We’ve therefore conducted a five year trial on women at high risk, where some women have taken an oestrogen blocker (tamoxifen) and some a dummy pill. The finding - supported by studies in other major centres internationally - is that you reduce breast cancer by 40 per cent on tamoxifen. However tamoxifen can cause womb cancer, clots, diabetes - all worrying side effects. So we are waiting to see the results over 10 years to see if the risk/benefit ratio for tamoxifen comes good.
"Meanwhile we’ve been trialling anastrozole on 6000 women with breast cancer, which also lowers oestrogen. We’ve found that these women do 20 per cent better than those on tamoxifen and have a reduced risk of developing cancer in the non-affected breast. Any woman with breast cancer has about twice the risk of getting it in the second breast. Tamoxifen reduces that by 50 per cent, but it looks as if anastrozole cuts the risk by about 80 per cent. If we can substantiate that finding it will be fantastic - a major breakthrough - because anastrozole doesn’t cause cardiovascular problems and it reduces strokes. We’ve now started a study comparing anastrazole to a placebo, and I only wish we could get the answer faster than five years. But we can’t. I’d feel pretty hopeless as a doctor if I didn’t conduct full randomised trials: we all remember the story of HRT which was rushed on to the market, without proper trials and billed as women’s great salvation, when it turned out to be quite the reverse. I’m never going to offer women an unproven treatment. It may help, but sorry! Until we know for certain - won’t prescribe it."
Watch Out For...
Gosarelin, an injected drug that switches off the periods of premenopausal women, and reduces their breast cancer risk by about 40 per cent. Tony explains that he is testing the effect of switching off the ovaries for two years to see if that’s enough to prevent subsequent breast cancer. "We have an ongoing study at the moment and we are also looking at the drug’s tolerability, which so far seems good. Women taking it do not report much change in sexual activity. They may have a few more flushes and sweats, but again the difference is not huge. The next discussion will be whether to proceed to an international trial, so again progress is slow. That’s the world of prevention for you.’
It Ain’t Over Till The Fat Lady Thins
While the most striking remedy for high risk women is scientific, surgical and specific, prevention for the majority of women could depend on simple lifestyle changes. It turns out that women bent on shedding the kilos are not swayed mere foolish vanity, but doing themselves a vital favour. New date analysis, says the Prof, has shown that gaining two stone between the ages 20 and 50 doubles a woman’s risk of cancer. Most weight gain occurs not, after the menopause, as is often thought, but between 30 and 50. It probably causes about 30 per cent of breast cancer and yet we can do something positive about it. Analysing data from the Iowa Women’s Study, it become evident that gaining weight in your thirties and forties is bad. Stop women putting on the pounds in those two vital decades and you’d probably halve breast cancer. It’s that simple."
Weight gain after diagnosis of breast cancer reduces survival
Anyone in the critical age group conscious of an expanded midriff can still take heart. Lose it before 50 and you can still cut your breast cancer risk rate 40 per cent. Slim down after 50 and you’re still boosting your odds, but less so, cutting the risk by 25 per cent. Weight gain after diagnosis of breast cancer reduces survival. Alcohol increases breast cancer risk too, but if you take folic acid, it reduces the risk again, as well as cutting your chances of getting cardiovascular disease."
An Inflammatory Story
The breast cancer plague won’t be over, it seems, till the fat lady thins. But why, scientifically do cells change in fat? "We’re involved in new research to work out the mechanism" says Tony, "but the best working hypothesis is that as you get fat you develop inflammation in the fat stores.
The inflammatory cells then make all sorts of nasty growth factors which stimulate breast cells to become cancerous. We also know that if you give non-steroidal, anti-inflammatory drugs (75m1 aspirin every day, or better still, we now believe, ibuprofen) you can reduce breast cancer by 30 per cent over 10 years, confirming the link with inflammation. Twenty per cent of cancers are caused by infection, for example heliobacter pylon can cause stomach cancer. That’s an inflammation too, so the hypothesis is very strong and very important because we can do something about it: fat causes inflammation, inflammation causes cancer. That’s why I’m intrigued by macrophages, which are the immune cells that go into inflammatory cells, into the fat in the breast and into actual tumours as well.’
Studying The Female Form
Tony Howell and Christie’s research dietitian, Michelle Harvie, have just completed a study on weight loss and exercise, which is currently still being analysed before the report stage. Women aged 3 5-45 who have lost weight are being checked for lower hormone levels and reduced density of breast tissue in mammograms.
Early results are promising
Early results are promising: hormone levels have indeed gone down and there’s been a marked reduction in abdominal fat (also linked to breast cancer) measured by MRI. So you really are what you eat? "The case for fruit preventing breast cancer is not strong" admits Tony Howell, "but the evidence is that if you eat more fruit you’ll eat less calories and it’s those fewer calories that can cut breast cancer.
There is an association between diet and cancer, but our view on this probably won’t be popular with those who support specific anti-cancer diets. The evidence for particular foods just is not there, though you might minimise animal fats and sugar. Our view is that it’s simply too many calories that cause disease. Not that I’m against choosing a particular diet - it gives you something to hang on to. But the bottom line is that people who don’t gain weight have much less cancer of the colon (if they are men) and breast (if they are women)."
Walk Away From Breast Cancer
Apparently we need not go for the burn or the super-advanced step class at a fancy gym. Fourteen studies have shown that even moderate exercise - walking briskly or running gently for 30 minutes five times a week reduces breast cancer.
Says Tony Howell, "It looks as if a five per cent weight loss coupled with two and a half hours of exercise a week is a winning formula. "Not all people who don’t exercise get cancer, of course. But they may get cardiovascular disease which is another inflammatory disease as is Diabetes type 2."
The Oldies Of Okanawa
Slimming your way out of cancer sounds so simple. But how often does a busy clinician like Tony Howell manage to get the message across to his patients? "I tell them a lot, actually" he stresses, "because honestly, eating healthily isn’t hard, it’s easy.
Look at me! I know what’s good for me, so on the whole I avoid animal fat and I try and eat less because all the evidence is that fewer calories mean you live longer without cancer.
We need to reduce calorie input and obesity in children
We need to reduce calorie input and obesity in children. Look at monkeys: there have been big studies on three monkey colonies in the States where they have lived longer on calorie restriction.
Look at Okanawa, where the people live longer and actually decide to eat less. Their culture is really fascinating "it’s naturally calorie restrictive, with some of every meal left on the plate. Admittedly there’s been no randomised trial, so their longevity could have some other cause, but in Okanawa, they have more centenarians than anywhere else in the world."
The Next Steps
"We may want to find ways to clock the effects of obesity, possibly blocking Coxl and Cox2, the enzymes that stop you producing prostaglandins which in turn produce inflammation. We need better ways to define women at high risk of cancer because the genetic link only affects some 5-10 per cent. Looking at a woman’s age of menopause, first pregnancy and other factors enables me to offer a risk asessment, but if your risk is pretty high, say one in six rather than the average one in nine, what you really want to know is am I the one, or am I the six? That’s a problem we need to solve, so that we only give drugs to those women who need them."
One in 10 women will develop breast cancer during her lifetime - but only until Professor Tony Howell’s statistical ambition is realised.
When that figure falls to none in 10, The UK’s first Professor of Cancer Prevention might be momentarily redundant, but he’d be more than well pleased. And judging by his lifelong passion for cells, and why they behave the way they do, Tony Howell would soon be off again, researching ways and means to close the door on other cancers.