Screening for Breast Cancer: A cruel deception
"For every complex problem there's a simple solution; and it's wrong"
Why do I have a problem with screening and why do I appear to be out of step with the agents of the State? This question really bothers me. I have devoted my professional life to women's health, I come from a family with a bad history of breast cancer, I've studied the disease for the best part of 30 years and still I don't get it! Perhaps it's because I have an unusual perspective on the subject?
For example unlike those who deliver the screening programme I am at the sharp end, picking up the pieces after a screen detected abnormality drives an innocent woman crazy with fear. I'm also fairly numerate having been the principal investigator of many multi-centre randomized trials of the treatment of breast cancer. Finally I was responsible for setting up one of the first screening centres in the UK following the Forrest Report in 1987. This centre at Butterfly Walk, Camberwell, South East London not only serves the local population but acted as the training centre for the whole of the SE of England. I know a bit about screening, so why my problem?
Public perception of risk
Each year we enjoy breast cancer awareness month or what I choose to call "Black October". Each October women are advised to practice breast self examination (a thoroughly discredited practice ) and are reminded that their risk of developing the disease is 1 in 11. This number is true only if a woman outlives all competing risks to reach the age of 85 with 25 out of 26 women dying of other causes. It is essential therefore that both doctors and the lay public understand the risk of developing breast cancer in the age groups invited for screening and understand the expectation of life after the diagnosis of breast cancer in the absence of screening in order to appreciate the absolute value of submitting themselves to screening.
However before we get into that I wish to describe some of the biases inherent in mammographic screening which support my somewhat counter-intuitive view that screening ain't all that it's cracked up to be.
Biases in Screening
Lead Time Bias: Say you get on a train to Edinburgh that crashes at Newcastle, then the duration of your fatal journey depends on your departure point. If you leave from Milton Keynes the journey lasts two and a half hours whereas if you leave from Kings Cross it is three hours... but you still die at the same time. In other words merely shifting the period of observation of breast cancer to the left might extend survival from the point of diagnosis without necessarily extending the duration of your life.
Length bias: If you were to trawl the sea for fish with a slow boat you'd catch the slow fish but miss those who can outswim your trawler. In other words if you trawl the female population for breast cancer at intervals you will catch the slow growing cancers that might be cured if allowed to grow to a clinically detectable stage whilst missing the rapidly growing cancers that appear in the intervals between screening and are probably the ones that will kill you in any case.
Class bias: Not all women invited for screening are "compliant" and graciously accept your invitation. The affluent upper classes who are health conscious tend to accept, whilst the poorer-educated lower classes may ignore your invitation or never get it in the first place because they maybe of no fixed abode. Futhermore we know that the outcome of treatment, stage for stage, is better amongst the better off so the apparent benefit of screening might just be a surrogate for class.
To get round these biases in order to truly assess the value of screening it is necessary to carry out randomized trials in whole populations with the outcome measure being breast cancer mortality. At the same time for all we know the intervention and its consequences might indirectly impact unfavourably on other causes of death. Ideally therefore the trials should be sufficiently well powered to look at all causes of death.
The trials of screening and relative risk reductions
There have been eight randomized or quasi-randomized trials of population mammographic screening for breast cancer and a number of observational studies which I will choose to ignore because of the biases described above. In addition there have been a number of attempts to conduct a meta-analysis of all these studies to improve the precision of the estimate. Finally there was the 2001 Cochrane review1, which attempted to weight the studies for quality before providing a summary statistic. Let us first dispose of the latter. This provoked the editor of the Lancet, Richard Horton to state, "At present there is no reliable evidence from large randomized trials to support mammography programmes". This then provoked the screening enthusiast to cry foul!
Whatever the merits or flaws in the Cochrane review there are a number of unassailable facts that emerge. The Canadian study, that produced a negative result, was the only one with individual randomization with informed consent. The HIP study New York, which produced the most favourable result, excluded 336 subjects in the control arm because of a past history of breast cancer compared with 853 in the screened population. The Edinburgh trial, which randomized according to postal district, ended up with huge imbalances in socio-economic factors favoring those invited for screening. Finally the largest effects were seen in the trials with the worst equipment and the longest screening intervals.
We therefore start off with the concern that screening has no proven effect.
Let's leave that for a moment and consider the more optimistic estimates produced by two overview analyses, Kerlikowske et al in 1995 and the US preventive services task force 2002. Neither could show a significant advantage for women under the age of 50 (in fact the latest result from the Canadian trial for the over 50 group actually showed a detriment for the first 10 years!) whereas their estimates for the under 50 age group varied between a hazard ratio of 0.76 (i.e. a relative risk reduction of 24%) and a hazard ratio of 0.84 (i.e. relative risk reduction of 16%) for breast cancer specific mortality. It is worth noting that most promotional material for screening includes a statement to the effect that screening will reduce the woman's risk of dying of breast cancer by 25%.
Let us now compute what that means in absolute terms so that an individual woman can work out her chances of benefit following a decade of mammographic screening. I can promise you that the numbers I describe are not in dispute but simply not offered up to the lay public.
The risk of a woman aged 50-60 for developing breast cancer is 2/1,000 a year or 2% over a decade(20 out of 1,000). The anticipated 10 year survival for clinically detected breast cancer in the absence of screening today is about 75%. Therefore we can expect 5 deaths per thousand women from breast cancer over this period (75% of 20). The relative risk reduction for screening applies to these 5 women. From the above overviews a realistic estimate would be the saving of 1 life (a relative risk reduction of between 16 and 24%). Therefore one in a thousand women stand to benefit from a decade of screening whilst 999 have to share the cost and by this I don't mean financial cost but the price in terms of "side effects".
This is what is meant by, "framing the result". Each year I play a little game with the senior postgraduate students at a course for specialists in breast cancer run by the Royal College of Surgeons of England. I tell them that there are two potentially effective screening tools for prostate cancer - one which will reduce their chances of dying from the disease by 20-30% whilst the other will save one life after 10,000 years of person screening. As a consumer or as a public health official which would you buy into? They all vote for the first and none vote for the second; yet if applied to breast cancer, they are the same. To continue marketing screening in terms of relative risk reduction in breast cancer mortality is disingenuous in the extreme.
The down side of screening
Of course if screening were as innocent an intervention as wearing seat belts or fluoridization of the water supply, then apart from opportunity costs, there wouldn't be a problem. However screening is by no means an innocent activity.
Like any other imperfect screening tool there has to be a balance between sensitivity and specificity. Sensitivity is a measure of the ability to detect those cancers present in the population whereas specificity is a measure of the accuracy of the screening tool. These two measures tend to pull in opposite directions. For 100% sensitivity i.e. not missing a single cancer, specificity will fall and many women with benign changes on mammography will be recalled for biopsy. There always has to be a delicate balance between these opposing needs, to catch all the cancers whilst protecting women without cancer from false alarms and unnecessary invasive procedures. Even at its best for every cancer detected another woman will have a false alarm. Whereas at its worst, fuelled by a fear of litigation, the cumulative risk of a false alarm over a decade of screening is around 40%.
All this unnecessary surgery has its morbidity but also tends to throw up pathology of borderline significance. The lay public can be forgiven in thinking that a pathologist can make a clear distinction between cancer and non-cancer, but sadly that is not the case. There is a whole spectrum of abnormalities ranging from epithelial hyperplasia with or without atypia, lobular carcinoma in situ, low grade duct carcinoma in situ (DCIS), high grade DCIS, micro invasive DCIS and tubular carcinoma of uncertain significance and unknown natural history. A conservative estimate would suggest that fewer than half of these would threaten a woman's life if left undetected and yet they account for 20% of "cancers" detected at screening. Furthermore many of these cases have field changes that affect the whole breast leading to a mastectomy for what might be a non-progressive condition. As a result the screening programme cannot claim that there is a net reduction of the mastectomy rate in the population, the opposite might be the truth.
Next there is the issue of "lead time". If the woman with the screen detected cancer is either doomed to die or at the other extreme diagnosed with a cancer that would have been curable even if left to develop to the point of clinical diagnosis, she will live as a "breast cancer patient" for one or two years longer than needs be.
Finally women invited for screening should be aware that the detection of DCIS with all the uncertainties described above might have an effect on the premiums for their health or life insurance. In fact I would go further and advise women intending to accept the summons for screening, at the same time they are buying a house, to postpone the event until after they've negotiated their mortgage.
Where do we go from here?
I believe that to carry on complacently now that we know the full costs and benefits of screening is NOT an option, so what should be done? In an ideal world I would recommend that we shut down the service and divert the resources (opportunity costs) to other issues to preserve the health of women. This might include improving the clinical care of women with symptomatic breast cancer as for example getting rid of the 12 week waiting list in some parts of our country for postoperative radiotherapy. We could also fund first class breast cancer research with the £50,000,000 a year so released. The promise of improved treatments holds more than improved screening which has nowhere to go.
Prevention of heart disease and osteoporosis would save more lives than the prevention of breast cancer yet the strategies could well be the same with the use of selective oestrogen response modifiers (SERMS).
However I see this as politically inexpedient so the best I could hope for here might be a shift in the screening window, to the 55-69 age group where sensitivity and specificity might be improved.
Finally if nothing else I believe there is an ethical imperative to offer women full informed consent with the risk and benefits spelled out in terms that don't patronize or deceive them. If after that the women vote with their feet - so be it.
Professor Emeritus of Surgery at University College London
Olzen O, Gøtzsche PC. Cochrane review on screening for breast cancer with mammography. Lancet 2001; 358: 1340 - 2.