I have served the NHS loyally for over 40 years and I feel that I deserve a campaign medal for every reorganization or new initiative I’ve faced, taken by governments of all political hues, but this latest one I regard as Nature’s way of telling me to resign my commission without facing another battle.

So by way of a swansong let me explain to our prime minister, whose political party my family has actively supported through three generations, why he might just want to take further advise on these new proposals.

First of all screening is not prevention of disease but detection of asymptomatic disease. Screening theory has it, that the detection of the earliest stages of a disease before it creates symptoms followed by prompt treatment might postpone death; but of course not prevent death. Death is inevitable like taxes and NHS reorganizations. Prevention literally means avoiding the onset of a specific disease and presupposes that we fully understand the aetiology of the disease in question. However the fundamental problem with both the prevention of disease and the early asymptomatic diagnosis of disease is that the whole population is exposed to an intervention and its unwelcome side effects for the benefit of a minority.

In contrast, cure of a disease, is targeted at the individual who reaps the benefits and “pays the price”. By “paying the price” I’m talking about inconvenience and toxic side effects rather than cash up front. In the practice of bedside medicine there is an ethical imperative of autonomy and informed consent. As a surgeon and an oncologist I have to inform the patient of the benefits versus the harms of my intervention whether it’s by surgery or the prescription of drugs. With the expansion of evidence based medicine (EBM) in oncology, we can do this with increasing precision and individualization. With the practice of public health interventions of screening and prevention the evidence base tends be less robust and the ethical model of respect for autonomy very poorly developed.

At one extreme of course, advice on healthy lifestyles that include the avoidance of tobacco products, regular modest exercise, plenty of fruit and vegetables and a little red wine, can indeed extend life expectancy [1] and enhance quality of life with little in the way of toxic side effects. Providing the government don’t become all sanctimonious about this, with thought police, exercise police, diet police, smoking police and withholding health care for “self inflicted” sickness, I have no problem with promoting such good advice. The problem though becomes much more difficult when the intervention is a test or a “treatment” or a “treatment” as the consequence of a test.

Before we can sanction these kinds of intervention we must have robust evidence from randomized controlled trials of large and representative populations, that the test or the treatment can reduce mortality from the disease with a favourable benefit/harm ratio, that is explicitly stated, to satisfy individual choice. In addition we need to be confident that the opportunity costs of such a programme don’t consume too many resources as to threaten the funding for treatment and cure of symptomatic disease. These are not the words of some maverick but can be taken as a summary of an excellent book, “Screening, evidence and Practice”, by Angela Raffle, consultant in public health and the National screening programmes and Sir Muir Gray, programmes director of the UK National screening committee 1996-2007. [2]

“Whereof one cannot speak, thereof one must be silent” stated Wittgenstein. Quite so Ludwig, but I can speak with authority about my own health and also about breast cancer.

To start with, my first hand experience can inform and illustrate the debate very nicely, as it describes the best of preventative action already available in the NHS, long before the PMs announcement. My youngest brother David died of a massive heart attack at the age of 59 whilst in office as President of the Royal College of Paediatrics and Child Health. After a period in mourning I took myself off to see my local GP, Dr. Chris Page, who counselled me on the harms and benefits of screening for risk of heart disease. He explained a risk assessment model factoring in family history, blood pressure, smoking history and blood lipid levels. He went on to explain how for each increasing increment of risk there were interventions of known toxicity that could modify this risk by a measurable quantity that could be described in absolute numbers rather than relative risk reductions. (See later) All of this was illustrated by coloured decision aid diagrams. I came to a well informed decision that it would be in my best interest to have my blood pressure monitored and my serum lipids measured. (Smoking advice was not required, I’d never started) My BP was mildly elevated as was my total cholesterol. For the last two years I’ve been taking a statin and a mild diuretic without toxic side effects. For this inconvenience I’ve perhaps reduced my risk of a myocardial infarct by about 1 in 10. [3] This experience illustrates the best of evidence based prevention within the NHS and I now wish to compare this with my knowledge of what’s on offer for women by way of prevention and screening for breast cancer.

 Most of my career has been devoted to the research and treatment of breast cancer and I have been in the front line in the development of screening and prevention of the disease. Furthermore my family has been afflicted with breast cancer making the challenge up front and personal. [4]

Let’s start with prevention. Most of the risk factors are beyond our control i.e. sex, age, race and genetic inheritance. Some risk reduction might be possible by adopting the healthy life style behaviours described above [1] together with the avoidance of binge drinking and if there is a choice in the matter, starting a family before the age of 30. However we are still searching for the holy grail of chemoprevention of breast cancer. In 1985 Jack Cuzick and I published a very important observation in the Lancet [5], describing how women, with breast cancer, treated with adjuvant tamoxifen demonstrated a significant reduction in the risk of a new breast cancer of the other breast. This observation was confirmed by other studies and led to the launch of the IBIS 1 trial for the prevention of breast cancer with tamoxifen amongst women at a high risk. This and similar trials confirmed that tamoxifen could lead to a relative risk reduction (RRR) in the incidence of breast cancer by more than 30% at the cost of some significant side effects.[6] This study provides an excellent example on how to calculate benefit/harm analyses that might inform public policy and allow the individual subject to judge for themselves.

For a start let me try and explain relative risk reduction.

Most statisticians and epidemiologists describe risks in relative terms such as 50% increase or 25% reduction. To translate this into simple numbers demands an understanding of the background risk. Let me provide a simple illustration. Say a young student is involved in field-work in Siberia and is keen to come home for Christmas but only has £300 to spend on air fares. A flight on BA would cost £500 but a flight on Air Uzbluchistan (AU) is within his budget. Just before he travels he learns that AU has a less that perfect safety record with a 50% increase in the chance of crashing compared with BA. To understand that risk, that sounds very alarming he needs to know BA safety record. He then learns that BA only crashes one in every 2,000,000 flights (i.e. risk is 0.000002%) a 50% increase in that risk is an extra 1:1,000,000 (i.e. an absolute risk of 0.000003%).

He can then judge whether he can accept that risk and will probably fly. In other words a 50% increase of a very small risk maybe a risk worth taking and the reverse is also true, that a 50% decrease of a very small risk is a very small gain.

Now let’s compute the absolute benefits of chemoprevention of breast cancer.

The normal risk for women is about 2:1,000 a year. The women in IBIS 1 had a background risk of about 3 times that, 6:1,000 a year or 6% in a decade. A 30%RRR would mean that about 2% might avoid breast cancer over a decade at the cost of increased hazard of thrombosis, endometrial cancer and other gynaecological problems. [6] In the USA it is commonplace to accept this trade off but as for myself, a co-author of the study, I don’t think the gain is worth the pain. Yet we still continue the search. The IBIS 2 trial is of a similar design but instead of using tamoxifen is using the aromatase inhibitor, anastrozole, which has been shown to be twice as effective as tamoxifen in preventing contralateral breast cancer with a much better safety profile. [7]

Who knows, that might be a preventative with a sufficient benefit harm ratio to win over the informed woman at increased risk of breast cancer.

Now let us adopt the same principle for mammographic screening for breast cancer.

Proponents of screening, often parade women who claim that, “screening saved their life”.  Most lay-people and screening zealots think that is the killer argument, well in a way it is. It kills of the debate at a stroke, not because it can’t be rebutted but because people like me find it difficult to be unkind. I believe the time is long past when we have to patronize womenfolk in order to retain our popularity.

Every woman can interpret her screening experience in a way that reinforces her decision to accept the invitation. The result was negative; thank God for the reassurance. The result was a false alarm; well you can’t be too careful.

The result showed duct carcinoma in situ (DCIS); thank God it was caught before it had a chance to spread. The result showed invasive cancer; thank God it was caught early.

Let us now re-examine those four scenarios.

Just how much reassurance is a negative result worth? For a start most women overestimate their risk of developing breast cancer. [8] If we stick with post-menopausal women, then the annual risk of developing breast cancer in a normal population is 2:1,000 a year and say, as in the UK, screening is at three yearly intervals then the accumulated risk over three years is 6:1,000. Therefore in each period 994:1,000 women might expect not to develop the disease. Assuming that the interval cancer rate (i.e. those cancers that develop between the first and second round of screening) is about a third of the screen detected rate, [9] then only an additional 4:1,000 woman over three years win extra reassurance.

In the second scenario no woman has a gain. It’s like thanking the fireman for rescuing you from the fire when he threw you in to begin with! This false alarm and unnecessary surgery is of no value to the woman. It can even be damaging in a subtle way, if as a chance finding the benign nodule or scar is close to an area of atypical ductal hyperlasia (ADH) or in situ lobular carcinoma, which then classifies the woman as at an increased risk, and then what does she do apart from worry?

The third scenario follows the detection of duct carcinoma DCIS. In about 30%-40% of such cases the disease is multi-focal and the woman is advised mastectomy for this “early” breast cancer. [10] Yet if left undetected some might regress and others might co-exist with the woman for the rest of her life. [11] Whenever a screening programme starts, 20% of the screen-detected cancers are DCIS and screening theory would suggest that their detection would ultimately lead to a fall in invasive cancers in the population. Not so; there is also a long- term increase in the incidence of invasive cancers. [12, 13].

 Finally the third scenario; yes indeed a life might have been saved. As I have described and also backed up by many others [14,15], the estimate of number of lives saved is about 1:1,000 per10 years of screening. (Note this is two orders of magnitude less than the benefits I described for the prevention of heart disease). Yet it does not follow that the screen detection of each cancer represents a life saved. If left to nature the cancer might have progressed slowly, became clinically obvious and cured by treatment on presentation. After all we are close to curing 75% of cases with modern therapy [16] and screening is good at detecting “good” cancers. It’s the bad cancers that slip through the net and appear as interval cases. [17] Furthermore some of the cancers are so slow growing that if undetected would never appear in a woman’s lifetime. These are what Welch describes as pseudo-cancers. [18] Last of all we never know for sure if indeed a life has been saved when mammography detects a cancer. A small grade III cancer even if node negative has a lethal capacity even if caught “early”. The biology of a tumour is more important than its chronology.

For too long the mantra of screening, “catch it early and we will save your life and save your breast”, has been allowed to unchallenged. Breast cancer is too complex a problem for such a facile solution. For too long women have been patronized and coerced into screening. And now the government want to extend the age for screening below the age of 50 in the face of the recently published UK trial that showed no significant advantage for this age group. [19]

I trust that the department of health will learn from the errors of the past and not be rushed into programmes of screening for prostate cancer, bowel cancer, ovarian cancer and other pathology without having evidence based harm/benefit analyses to offer the individual to allow them an informed choice. If they decide no thank you, so be it. In discussing the ethical issues of screening we must accept a tension that exists between “Utilitarian” principles and those of “Autonomy”. Utilitarianism involves social engineering for the “greatest good of the greatest number”, whereas autonomy assumes the individual has an informed choice when health interventions for “their own good” are considered. Social engineering and coercion might be acceptable for hygiene and substance abuse, but when the balance of benefit versus harm is a close call then surely the right to self -determination trumps the principle of utilitarianism. Nowhere is this truer than in the area of screening for cancer. We screen for cancer to reduce cause-specific mortality without an increase in all cause mortality and at an acceptable cost in terms of medical morbidity. Even where their is level one evidence from RCTs of a reduction in cancer specific mortality, the benefit in absolute risk reduction maybe so small that the individual should have the right to make a personal trade off against the undoubted harms of false alarms, over-diagnosis and radical treatments for diseases that, if left to nature would never announce themselves in a lifetime. I therefore propose that the uncritical promotion of screening is unethical by modern ethical standards and reflects a paternalistic attitude that would be unacceptable for treatment aimed at curing established disease. In these cases cure is better than prevention.

[1] Khaw KT, Wareham N, Bingham S, Welch A, Luben R, Day N Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study..PLoS Med. 2008 Jan 8;5(1):e12 [Epub ahead of print]

[2] Screening Evidence and Practice. Angela Raffle and Muir Gray, Oxford University Press, Oxford 2007

[3] Fidan D, Unal B, Critchley J, Capewell S.   Economic analysis of treatments reducing coronary heart disease mortality in England and Wales, 2000-2010.QJM. 2007 May;100(5):277-89.

[4] Baum M A lifetime in breast cancer research. Eur J Cancer. 2007 Jul;43(10):1496-7

[5] Cuzick J, Baum M.  Tamoxifen and contralateral breast cancer.  Lancet 1985;ii:282

[6] Cuzick, J., Forbes, J., Edwards, R., Baum, M., Cawthorn, S., Coates, A., et al., First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet, 2002. 360(9336): p. 817-24.

[7] Howell, A., Cuzick, J., Baum, M., et al., Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet, 2005. 365(9453): p. 60-2.

[8]  Black W.C., Nease R.F. Jr., Tosteson A.N. Perceptions of breast     cancer risk and screening effectiveness in women younger than 50 years of age. Journal of the National Cancer Institute 1995;87:720-731.

[9] Blanks RG, Moss SM, McGahan CE, Quinn MJ, Babb PJ. Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990-8: Comparison of observed with predicted mortality. BMJ 2000; 321:665-9.

[10] NHS cancer screening programmes. NHS Breast Screening Programme & British Association of Surgical Oncology Breast Group. An audit of screen detected breast cancers for the year of screening April 1999 to March 2000.16-5-2001.

[11] Collins LC, Tamimi RM, Baer HJ, Connolly JL, Colditz GA, Schnitt SJ Cancer. Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy. Cancer 2005 May 1;103(9):1778-84.

[12] Zackrisson S, Andersson I, Manjer J and Garne JP, Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow up study. BMJ 2006;332:689-92

[13] Møller H, Davies E, Over-diagnosis in breast cancer screening. BMJ 2006; 332: 691-692

[14] Miller AB. The costs and benefits of breast cancer screening. Am J Prev Med 1993;9:175-80.

[15] Sarfati D. Howden-Chapman P. Woodward A. Salmond C. Does the frame affect the picture? A study into how attitudes to screening for cancer care are affected by the way benefits are expressed Journal of Medical Screening 1998; 5(3):137-140.

[16] Vervoort MM, Draisma G, Frachebaud J, van de Poll-Franse, de koning HJ (2004). Trends in the usage of adjuvant systemic therapy for breast cancer in the Netherlands and its effect on mortality. Br J Cancer 91: 241-247.

[17] Watmough D.J.[1993] Interval Breast Cancers. American J Roentgenology July 1993, 161, 3.

[18] H.Gilbert Welch, “Should I be tested for Cancer?”

University of California Press, 2004, ISBN 0520239768

[19] Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L, for the Trial Management Group. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet 2006;368:2053-60.