Abstract
It is an accepted principle of clinical practice that any intervention should be preceded by informed consent demonstrating that the individual understands both the potential benefits and harms of that intervention. I believe that this principle has been neglected when women are invited for mammographic screening. Public health agencies promote screening as an unequivocal ‘good’ by publicizing the benefit in mortality reduction in relative terms and avoiding discussion of potential harms. Each woman is encouraged to believe that, whatever the outcome of her individual screening experience, she has in some way benefited. I believe that the harm:benefit margins for screening are finely balanced and that the individual woman should be able to make an informed choice based on the balance of benefit versus harm for an individual, rather than for the total population of women in the screening age group.
I often introduce myself as a son of a mother, a husband of a wife, a brother of a sister, a father of two daughters and an uncle to seven nieces. My mother died tragically from breast cancer and my sister is a long-term survivor. My family is judged to be at high risk and I want the best for them.
Furthermore, I know a lot about screening for breast cancer having established the first unit in South East England in 1987 whilst I was Professor of Surgery at Kings College Hospital (London, UK) and later served on the national screening committee for 9 years. I therefore believe I can speak with some authority on the subject. I find that kind of disclaimer increasingly important because of the unpopularity of my views.
The nature of informed consent
I am sure all clinicians can agree from the start that in the name of autonomy, women should be treated as adults and allowed to make informed choices about any interventions that might affect their health [1]. To make an informed choice implies that the women in question are appraised of both the potential benefits and harms, described in a way that is accessible and meaningful. It is therefore essential that the lay woman understands the nature of ‘risk’ and ‘relative risk’. 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 Best British Airways (BBA) would cost £500, but a flight on Air Uzbluchistan (AU) is within his budget (please note that BBA and AU are fictional airlines). Just before he travels he learns that AU has a less than perfect safety record with a 50% increase in the chance of crashing compared with BBA. To understand that risk, which sounds very alarming, he needs to know BBA's safety record. He then learns that BBA only crashes one in every 2 million flights (i.e., risk is 0.00005%) a 50% increase in that risk is an extra 1:1 million (i.e., an absolute risk of 0.000025%).
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 is still a very small risk.
Real examples concerning women's health might include; the pros and cons of hormone replacement therapy (HRT), the selection of adjuvant chemotherapy after surgery for breast cancer and screening for the disease by mammography. In each case the benefits and harms are usually expressed in relative risk; for example the extra risk of developing breast cancer on HRT or the reduction in risk of death from breast cancer after therapy or after screening. To be translated into absolute terms requires an understanding of the background risk. Women equipped with this knowledge can then make an individual and informed decision to accept or reject the offer.
Examples of relative risk in women's health
Adjuvant chemotherapy after surgery for breast cancer is associated with an approximate 25% reduction of the risk of dying in premenopausal women, but only approximately half that in postmenopausal women, where hormone therapy is much more effective [2]. The calculations to translate this into absolute benefits demand a knowledge of the prognosis for the individual cancer based on stage, grade and hormone receptor status, and also knowledge regarding competing risks of death from comorbidity. These calculations are, in fact, too complicated for the average clinician, let alone the lay woman, but she can expect the specialist to work out the numbers for her using a ‘decision aid’ such as ‘ADJUVANT online’ [101]. For the average postmenopausal woman diagnosed with breast cancer, cytotoxic chemotherapy might be associated with a 1.0% additional chance of living for 10 years to be traded off against the toxicity (i.e., an improvement from, for example, 75 to 76% 10-year survival) [101]. Many women would grasp this straw, but for other women with different fears and values the choice might be to decline the offer of her oncologist.
As far as HRT is concerned, a relative risk for breast cancer incidence after long-term exposure of, for example, 1.3 [3], translates to an extra six cases of breast cancer for 1000 women over 10 years (i.e., 20–26/1000). In addition, these extra cases seem to carry a better prognosis. Women with uncontrollable climacteric symptoms might happily accept that risk for a better quality of life.
However, as is always my experience, when applying the same approach to mammographic screening, radiologists and lay women, who have been conditioned for decades to believe that screening is an unquestionable virtue, cannot understand why any woman would be so foolish as to fail to accept her invitation when the caravan rolls into the local supermarket parking lot.
The true benefits & harms of screening by mammography
Many of us believe that much of the drive for population-based screening is politically motivated, whereas the calculations I always offer when women consult me on the subject in my private office are based on the individual need for informed choice [4,5]. 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, which, in a way, it is. It kills off the debate at a stroke, not because it can not 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. Well it's not as easy as that. Let us 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 [6]. If we stick with postmenopausal women, then the annual risk of developing breast cancer is 2/1000 a year and say, as in the UK, screening is at 3-year intervals, then the normal risk is 6/1000. Therefore, in each period 994/1000 women might expect not to develop the disease. Assuming that the interval cancer rate (i.e., those cancers that develop after a negative screen in the interval to the next screening round) is approximately a third of the screen detected rate [7], then only an additional 4/1000 woman over 3 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, then what does she do apart from worry?
The third scenario follows the detection of DCIS. In approximately 30–40% of such cases the disease is multifocal and the woman is advised mastectomy for this ‘early’ breast cancer [8]. However, if left undetected some might regress and others might coexist with the woman for the rest of her life [9]. Whenever a screening program 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 [10,11]. Welch and his colleagues argue that this might be as many as 1 in 4 [12], whilse Gøtzche and colleagues took these numbers to argue that published estimates of harm:benefit ratios were five-times too optimistic [102].
Finally the third scenario; yes indeed a life might have been saved. As I described and also backed up by many others [13,14], the estimate of number of lives saved is approximately 1/1000 per 10 years of screening or even lower if one accepts the US preventative task force estimate of a 17% relative risk reduction [15] (note this is an order of magnitude less than the worse-case scenario for adjuvant systemic chemotherapy discussed above). 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, become clinically obvious and been 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 is 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 pseudocancers [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 tumor is more important than its size [19,20].
Conclusion
For too long the mantra of screening, ‘catch it early and we will save your life and save your breast’, has been allowed to go unchallenged. Breast cancer is too complex a problem for such a facile solution. For too long women have been patronized and coerced into screening. Hazel Thornton, a lay activist, was one of the first to catch on to this cruel deception, so I shall allow her the last word, because in the end it is our womenfolk who will have to choose between scarce resources being spent on screening that will only help 1 in 10,000/year versus investment in better treatment that will benefit most of the women who develop the disease.
“If breast screening is to move on, then it is time the proponents of breast screening moved on, not just to the future, but to the present. Women today do not want to be patronized, or fobbed off with unbalanced, insufficient information, but to be treated with respect, so that they can make up their own minds. Decision-making, to give proper consent, requires good-quality information. It is evident that they are not getting it” [21].
Future perspective
I believe that unselected population screening by mammography has a great future behind it. Over the next 5–10 years we should be able to identify the 25% of the population that accounts for 75% of the breast cancer burden. This will be possible through better genotyping combined with demographic profiling. Furthermore, x-ray mammography may well be replaced by magnetic resonance imaging (MRI) scanning, which will not only reduce the hazard of the technique but increase the sensitivity. These developments will influence the harm:benefit ratio in a favorable direction. At the same time, improvements in treatment will narrow the margins within which screening operates, further pushing the technology towards identifying and screening those at most risk of developing the most aggressive types of the disease. Inevitably there will come a point when the predictive power for risk will be so great that prophylactic mastectomy as a choice would have to be balanced against MRI screening, as we are already seeing young women carrying breast cancer, early onset (BRCA)I/II mutations. Finally, the potential for the chemo-prevention of breast cancer combined with better treatment are likely to make all screening redundant, and I believe future historians will look upon screening as intermediate technology.
Executive summary
Informed choice is an ethical imperative before all medical interventions.
Public health interventions have often overlooked this principle.
Mammographic screening for breast cancer has significant harms as well as benefits.
Women invited for screening are induced to comply by promoting the benefits in terms of relative risk reduction for breast cancer mortality, whilst the down side of false alarms, overdiagnosis of borderline pathology and ‘pseudocancers’ are seldom mentioned.
Women are encouraged to interpret each screening experience in such a way as to reinforce the public health agenda.
Women should no longer be patronized in this way but should be allowed full informed consent by full disclosure of benefits and harms expressed in absolute values for the individual, rather than relative values that apply to the whole population.