An in-depth review of randomised trials on screening for breast, colorectal, cervical, prostate and lung cancers, shows that the benefits of mammographic screening are likely to have been overestimated. This overestimation results from the use of an unconventional statistical method which differs from that used for other cancer screening trials, concludes the paper co-authored by researchers at King’s College London and the University of Strathclyde Institute of Global Public Health at iPRI, France.
Started in the 1960s and 70s, the Swedish randomised trials suggested that mammography screening could reduce breast cancer mortality by 20 to 25% in populations where screening is widespread. These findings were, and remain, extremely influential in decisions taken to establish population breast cancer screening programmes using mammography.
The goal of cancer screening is principally to reduce the mortality from the disease in question by enabling cancers to be found at an early stage. Early detection reduces the risk of being diagnosed with an advanced cancer that is often deadly. In 2002, World Health Organisation recommended that when population screening for breast cancer was implemented in any region, the rate of advanced breast cancers should be monitored: if the programme is successful, these rates should show a fall over time indicating that mammography screening is contributing effectively to reducing breast cancer mortality. Moreover, with increased screening, more rapid and more pronounced falls in breast cancer mortality would be expected in countries that implemented mammography screening programmes at end of the 1980s than in countries that implemented programmes ten to fifteen years later.
“Contrary to expectations, numerous studies in North America, Europe and Australia have shown that the rates of advanced breast cancer have not declined in countries where most women regularly attend mammography screening” observed Professor Philippe Autier, lead author from University of Strathclyde Institute of Global Public Health at iPRI. He went on to note that “other studies have shown that declines in breast cancer mortality were the same in countries that implemented mammography screening end of the 1980s as those that did so ten to twenty years later. The absence of differences in mortality reductions could not be explained by differences in access to modern therapies.”
Professor Richard Sullivan, from the Institute of Cancer Policy, King’s College London observed that “these findings were in sharp contrast with screening for cervical and colorectal cancers, two cancers for which studies have clearly shown the capacity of screening to reduce the numbers of advanced cancers in populations. This has major implications for policy-makers in middle income countries who are now making decisions about where to prioritise cancer screening efforts”.
These discrepancies led Autier and his colleagues to undertake an in-depth review of all randomised trials of cancer screening. Autier concluded that “if the Swedish trials had used similar statistical analyses to other cancer screening trials, reductions in the risk of breast cancer death associated with mammography screening would have been much smaller, probably less than 10%.”
“The reduction seen in the mortality from breast cancer in many countries is one of the major contributions to Cancer Control in recent times” noted Peter Boyle, professor and director of the University of Strathclyde Institute of Global Public Health at iPRI. “Many factors have contributed to this success including earlier presentation and better diagnosis, as well as major improvements in the organisation of care (multidisciplinary teams) to specifc improvements in surgery, radiotherapy and chemotherapy/endocrine therapy. Currently, assessment of the impact of mammographic screening programmes cannot be made without taking advances in breast cancer treatment into account.”
Objectives: We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials.
Participants: Men and women from 30 to 74 years of age.
Setting: Randomised trials on cancer screening.
Design: For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death.
Main outcome measures: Relative risk of cancer death.
Results: In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening.
Conclusions: The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups.