INTRODUCTION:

Eight trials examining the performance of screening mammography have been conducted in the USA, Sweden, the United Kingdom and Canada, beginning in 1963. A first report by the Conseil d'évaluation des technologies de la santé (CETS) published in 1990 concluded that screening mammography trials had shown reductions in mortality from breast cancer of 35%, with 45% in the subgroup of women aged 50 to 69. A second report in 1993 concluded that mammographic screening of women under 50 had not been shown to reduce mortality. By the year 1998, when Québec introduced the Programme québécois de dépistage du cancer du sein (PQDCS), all Canadian provinces and many other countries had organized screening programs in place. A recent Cochrane Collaboration Group review, challenging the belief that mammography screening is an effective tool for reducing breast cancer deaths, has raised concerns about the validity of the published randomized trials. This update addresses three questions (1) What is the strength of the scientific evidence on which screening mammography programs are based? (2) What is the evidence in support of screening for women aged 40 to 49 years? (3) What are the implications of research studies for maximizing the effectiveness of modern programs such as the Programme québécois de dépistage du cancer du sein (PQDCS)? METHODOLOGIC

ANALYSIS:

An evaluation of efficacy trials essentially aims to determine whether the conditions under which the trials were performed and the results that were obtained can guide strategies. In practice, the reference strategy (no screening) may include some uncontrollable screening activities, which will weaken the contrast with the screening intervention. A valid study must be a fair comparison between screening and no screening. Thus screening and control cohorts should have the same baseline risk of breast cancer mortality, should be treated equally in all regards except concerning the screening or control intervention, and should have the information on their outcome measured in a way that is independent of their assignment to the screening or control group. Validity can be compromised by bias of known direction and by bias of unknown direction. In this evaluation, to further develop the notion of bias of known direction, we use the concept of strength of contrast. It corresponds to the degree to which a trial succeeds in bringing out the divergence between the two strategies compared and in measuring the effects that this divergence produces. Five elements are evaluated in this report which help assess the strength of contrast -the technical contrast, or the nature of the difference between screening and control interventions; -the era in which these techniques are applied; -the quality of the intervention, including quality control measures; -rates of participation and contamination measured among screening and control cohorts; and -the timing of the measurement of the effects of screening on mortality (or timing dilution). DISCUSSION AND

CONCLUSIONS:

Question 1 What is the strength of the scientific evidence on which screening mammography programs are based? There are serious concerns regarding the validity of most of the trials supporting mammography screening, based on methodological weaknesses in the screening trials. Studies are highly heterogeneous with regard to the strength of the contrast that they studied, with numerous weaknesses identified in all the major studies, meaning that the potential of screening mammography has perhaps not been thoroughly explored. Using the best available data, one can conclude that there is fair evidence of moderate reduction of breast cancer mortality, of the order of 9 to 15%; data restricted to women over the age of 50 show greater reductions, of the order of 24 to 29%. Furthermore, our analysis has demonstrated that modern mammography, carried out under quality conditions that maximize its performance, has the potential to identify cancerous lesions earlier in their progression, and this may allow for some further reduction in mortality.

Conclusion:

Existing scientific trials, despite their flaws, support mammography screening programs. In addition, there are good reasons to believe that modern, well-conducted screening programs may achieve earlier detection and diagnosis of breast cancer and, perhaps, greater reductions in breast cancer mortality than what has been found in screening trials. Question 2 What is the evidence in support of screening mammography for women aged 40 to 49 years? There is much less data available to answer the question, since most study experience is in women over 50, even though some women in some of the studies started screening several years earlier than their fiftieth birthday. The best data available show no significant reduction in breast cancer mortality in women screened before the age of 50. In the absence of any convincing data that mammography is efficacious in this age group, harmful effects may outweigh any positive effects.

Conclusion:

Trial data published to date do not provide scientific justification to recommend screening for women younger than 50. However, this conclusion does not exclude the possibility that screening of individual women, based on a personalized risk assessment, could be of benefit. These conclusions should be reviewed when results from the UK Trial become available. Question 3 What are the implications of research studies for maximizing the effectiveness of modern programs such as the Programme québécois de dépistage du cancer du sein (PQDCS)? Although the PQDCS already includes rigorous control of the quality of films produced, certain aspects of the structure and process of trials examined under the rubric of strength of contrast can be transposed as additional quality norms. Notable among these are double reading of films and an annual reading volume sufficient to allow each radiologist to acquire and maintain the necessary expertise to detect breast cancer in its early stages. These aspects should also allow for a reduction in false positive rates and subsequent unnecessary diagnostic procedures. Moreover, high participation rates at each screening round will contribute to achieving and perhaps exceeding the mortality reductions obtained by screening trials.

Conclusion:

Modern screening programs such as the PQDCS may produce outcomes comparable or even superior to those observed in screening trials if they achieve a standard of quality equal to or better than the standard achieved by trials. Measures that should reduce false positive rates and assure high-quality screening include making sure that high-quality mammographic films are being produced, that readers have the necessary expertise to detect early cancer and avoid false positives, and double reading of a proportion of films. While participation rates should be as high as possible, efforts to increase participation should not overstate the benefits of mammography nor understate the risks and uncertainties which remain.