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Abstract
The latest publication in the International Agency for Research on Cancer's (IARC)
series of Handbooks of Cancer Prevention is focused on breast cancer screening. The
monograph is the outcome of a weeklong meeting of the Working Group on the Evaluation
of Cancer-Preventive Strategies that took place in Lyon, France, March 5–12, 2002.
The decision to produce a handbook on breast cancer screening was timely for several
reasons. First, only a few monographs exist that focus exclusively on breast cancer
screening, none of which represent a comprehensive treatment of the subject, and all
were published before 1990 [1-4]. Second, the value of breast cancer screening recently
had been challenged by a Cochrane Review [5] on screening for breast cancer with mammography,
and a number of independent expert groups had been assembled to evaluate that analysis
and the authors' provocative conclusions. Thus, in the presence of another expert
group's conclusion that there was no scientific evidence to support the value of mammography,
the IARC Working Group's evaluation of the world's literature on the efficacy of breast
cancer screening had an extra dimension of drama. Contrary to the Cochrane Review,
the IARC Working Group affirmed the value of mammography for women aged 50–69.
Anyone interested in breast cancer control, or screening in general, will find this
volume a valuable addition to their library. The book is well organized, and proceeds
through the evaluation of the scientific evidence in the context of the classic criteria
for principles and practices of screening for disease established by Wilson and Junger
in 1968 [6]. Chapters one through three describe the global burden and the natural
history of breast cancer, conceptual considerations related to screening performance,
various methods of early detection, including conventional and experimental imaging
techniques as well as physical exams, and use of screening and behavioral issues related
to screening uptake. Chapters four through six review conceptual issues and the existing
evidence on efficacy, effectiveness, and cost-effectiveness of screening. The monograph
concludes with a summary chapter, an additional chapter with a brief description of
the conclusions, and another on recommendations for future research. Thus, the monograph
provides the most extensive treatment available of the issues pertaining to breast
cancer screening. It concludes that mammography is effective in reducing breast cancer
mortality, but like other screening tests, has a number of limitations.
Undoubtedly, those who are familiar with the literature will see some topics that
are treated with a degree of certainty that belies the limitations of the existing
data, or the presence of alternative interpretations. If one accepts the results from
the trials uncritically it is reasonable to conclude that there is limited evidence
to support the efficacy of screening women aged 40–49. However, the poor performance
of screening in the trials in this age group must be seen as the result of screening
intervals that were too wide to achieve a measurably reduced incidence rate of advanced
disease. Considerable inferential evidence from the trials [7], meta-analyses [8,9],
and evaluations of service screening [10-12] support the conclusion that, when women
in their forties are screened at a 12–18 month interval, mortality reductions are
equivalent to those that can be expected in women aged 50+ screened every 24 months.
Another example of a conclusion that has limited supporting evidence is the assertion
that 5–25% of cancers detected by mammography represent over-diagnosis. While it has
been estimated that some over-diagnosis exists, the overall proportion likely is less
than 5%, of which most occurs during a prevalent screen. In subsequent incident screens
the rate is very small to nonexistent [13,14].
Like many areas of research, experts can and will differ in the conclusions they draw
from existing evidence. Still, the IARC Handbook on Breast Cancer Screening has much
to offer, and will be required reading for anyone with an interest in screening, and
especially an interest in breast cancer screening.
Competing interests
None declared.
Abbreviations
IARC = International Agency for Research on Cancer.
The long term effect of mammographic service screening is not well established. We aimed to assess the long-term effect of mammographic screening on death from breast cancer, taking into account potential biases from self-selection, changes in breast cancer incidence, and classification of cause of death. We compared deaths from breast cancer diagnosed in the 20 years before screening was introduced (1958-77) with those from breast cancer diagnosed in the 20 years after the introduction of screening (1978-97) in two Swedish counties, in 210000 women aged 20-69 years. We also compared deaths from all cancers and from all causes in patients diagnosed with breast cancer in the 20 years before and after screening was introduced. In the analysis, data were stratified into age-groups invited for screening (40-69 years) and not invited (20-39 years), and by whether or not the women had actually received screening. We also analysed mortality for the 40-49-year age-group separately. The unadjusted risk of death from breast cancer dropped significantly in the second screening period compared with the first in women aged 40-69 years (relative risk [RR] 0.77 [95% CI 0.7-0.85]; p<0.0001). No such decline was seen in 20-39 year olds. After adjustment for age, self-selection bias, and changes in breast-cancer incidence in the 40-69 years age-group, breast-cancer mortality was reduced in women who were screened (0.56; 0.49-0.64 p<0.0001), in those who were not screened (0.84 [0.71-0.99]; p=0.03), and in screened and unscreened women combined (0.59 [0.53-0.66]; p<0.0001). After adjustment for age, self-selection bias, and changes in incidence in the 40-49-year age-group, deaths from breast cancer fell significantly in those who were screened (0.52 [0.4-0.67]; p<0.0001); and in all women, screened and unscreened combined (0.55 [0.44-0.7] p<0.0001) but not in unscreened women (p=0.2). In both 40-69-year and 40-49-year age-groups, reductions in deaths from all cancers and from all-causes in women with breast cancer were consistent with these results. Taking account of potential biases, changes in clinical practice and changes in the incidence of breast cancer, mammography screening is contributing to substantial reductions in breast cancer mortality in these two Swedish counties.
The efficacy of mammographic screening in the reduction of breast carcinoma mortality has been demonstrated in randomized controlled trials. However, the evaluation of organized screening outside of research settings (so-called "service screening") faces unique methodologic and conceptual challenges. The current study describes the evaluation of organized mammography screening in a clinical setting and demonstrates the benefit obtained from service screening in two Swedish counties. In the group of subjects ages 20--69 years, there were 6807 women diagnosed with breast carcinoma over a 29-year period in 2 counties in Sweden and 1863 breast carcinoma deaths. All patients were classified from patient charts based on their screening status (i.e., whether they had been invited to undergo screening and whether they actually had undergone screening). The number of women who lived in the 2 counties during the 29-year study period was provided by the Central Bureau of Statistics. Breast carcinoma-specific mortality was compared across three time periods: 1) 1968--1977, when no screening was taking place because mammography had not been introduced; 2) 1978--1987, the approximate period of the Two-County randomized controlled trial of screening in women ages 40--74 years; and 3) 1988--1996, when all women in the 2 counties ages 40--69 years were invited to undergo screening (service screening). When comparing breast carcinoma mortality in screened women with that in women diagnosed before screening was introduced, a correction for self-selection bias was incorporated to prevent overestimation of the benefit of screening. The mortality from incident breast carcinoma diagnosed in women ages 40-69 years who actually were screened during the service screening period (1988--1996) declined significantly by 63% (relative risk [RR] = 0.37; 95% CI, 0.30--0.46) compared with breast carcinoma mortality during the time period when no screening was available (1968--1977). The mortality decline was 50% (RR = 0.50; 95% CI, 0.41--0.60) when breast carcinoma mortality among all women who were invited to undergo screening (nonattendees included) was compared with breast cancer mortality during the time period when no screening was available (1968--1977). The reduction in mortality observed during the service screening period, adjusted for selection bias, was 48% (RR = 0.52; 95% CI, 0.43--0.63). No significant change in breast carcinoma mortality was observed over the three time periods in women who did not undergo screening. This group included women ages 20--39 years because these individuals were never invited to undergo screening, and women ages 40--69 years who did not undergo screening (not invited during the randomized trial or invited during the second and third time periods but declined). Regular mammographic screening resulted in a 63% reduction in breast carcinoma death among women who actually underwent screening. The policy of invitation to organized screening with mammography appears to have reduced breast carcinoma mortality by 50% in these 2 counties. Copyright 2001 American Cancer Society.
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