Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends

Jørgensen and colleagues (2009a,b,c) have often questioned the value of mass screening by mammography claiming that most of the reduction in mortality from the disease observed in the UK after the introduction of screening was due to a generalised shift towards earlier detection of symptomatic tumours and access to good quality treatment brought about by the programme and the publicity that accompanied its implementation. They argue that the value of detecting and treating sub-clinical tumours has been overestimated (Gøtzsche et al., 2009) while harms induced by screening are underestimated. Harms include anxiety in women who have a false positive exam but also, of greater concern, the distress and consequences of treating the tumour in women who would have died from other causes before their breast cancer would have progressed to clinical relevance (Jørgensen et al, 2009b).


There is general agreement that modern therapies for early symptomatic breast cancer improve survival and can reduce disease-specific mortality. The widespread adoption of mammographic screening since the 1980s and the introduction of organised population-based screening programs have brought substantial improvements in awareness and access to quality breast health services for the population at large, not confined to the age group undergoing screening. This may well explain the early impact on mortality rates which, as Jørgensen and colleagues (2009a) argue, occurred too early to be attributed directly to the mammography exam itself. Resolution in this debate is particularly important for countries where breast cancer incidence is low and more compelling priorities limit resources that can be devoted to this disease. Clearly, control of breast cancer in these settings should start by making early diagnosis of clinically detectable tumours and quality treatment available to all cases.


But acknowledging the value of down-staging–reducing the proportion of cancers presenting at stage III or IV when prognosis is poor– does not imply that mammography has no net effect over and above the early detection of palpable tumours. All randomised trials of mammography, except the Canadian trial, showed a benefit to differing extents (depending on when and where they were conducted) of advanced diagnosis of palpable tumours, but none lasted long enough to measure the long-term impact on mortality of treating sub-clinical tumours that are detected only by mammography. It is likely that the lead time of such tumours is much longer than the 2.4 years adopted by Duffy et al. (2008). If this is the case, the full impact of mass screening in the UK and in other regularly screened populations has begun to be manifest only in recent years. The latest reported incidence estimates for the UK showed a decline in 2006 in the age-group 50-64 years targeted for screening since the beginning of the programme (Cancer Research UK, 2009). If this decrease persists, it might be indicative of the fact that invasive cancers were being prevented by treating in situ tumours. Weiss (2007) suggested that the decline in the incidence of invasive breast cancer in American women aged 40-49 years, between 1975 and 2002, could be a consequence of treating screen-detected in situ cancers that had been increasing rapidly in the same time period in that age group.


Many factors contribute to time trends in breast cancer incidence including varying screening intensity, modality, coverage as well as changes in the prevalence of late-stage promoting factors such as hormone replacement therapy. It is difficult by ecological analyses alone to interpret such trends, let alone to quantify the effects of the factors involved. A more reliable quantification of the long-term effects of screening will be soon available from on-going studies of time trends by screening history that link incident cases and deaths with information from screening registries.


The concern about the excess incidence caused by screening is that some of those tumours would have not progressed to a clinical stage in the woman’s lifetime. Some women would therefore suffer the distress of treatment with no benefit. However, around 1980, before the introduction of screening, half of the cases of breast cancer occurred in women younger than 65 years (figure); in 1985 British women aged 50 years were expected to live on average 30 more years (Office for National Statistics, 2009); the majority of women who were the target of screening were therefore destined to live for another two decades at least. The figure shows for comparison the incidence of prostate cancer, a disease for which screening with prostate-specific antigens is much more controversial. The age at which the incidence of prostate cancer in men begins to rise steeply is 20 years older than that seen for the rise in female breast cancer cases; moreover the prevalence of sub-clinical tumours of the prostate is at least one order of magnitude greater compared with the female breast. These observations suggest that for prostate cancer the proportion of screen-detected men who would not likely benefit from early diagnosis and treatment is much greater than for women with early breast cancer.

From what we know of the natural history of breast cancer, most malignant tumours progress to a life-threatening stage sooner or later. At present we do not have reliable information on how long that takes in order to quantify the balance between harms (unnecessarily treated tumours) and benefits (saved lives). What we do know is that mortality from breast cancer in the UK has never been lower since 1950. With all-causes mortality rates falling and increasing life-expectancy in the UK (Office for National Statistics, 2009), more and more of those screen-detected tumours that Jørgensen and Gøtzsche (2009) today count as over-diagnosed and unnecessarily treated may be counted as lives saved tomorrow.