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Background. Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women. Various possible reasons have been suggested for this, but none firmly is established. Methods. The Swedish Two‐County Study is a randomized trial of breast cancer screening of women aged 40‐74 years, comprising with 133,065 women with a 13‐year follow‐up of 2467 cancers. The Breast Cancer Detection Demonstration Project (BCDDP) is a nonrandomized screening program in the United States, with a 14‐year follow‐up of 3778 cancers in women aged 40‐74 years. The Swedish results by age were updated. The lesser effect of screening at ages 40‐49 years was investigated in terms of sojourn time (the duration of the preclinical but detectable phase) size, lymph node status, and histologic type of the tumors diagnosed in the Swedish Study and their subsequent effect on survival using survival data from both studies. Results. In the Swedish Trial, a 30% reduction in mortality associated with the invitation to screening of women aged 40‐74 years was maintained after 13‐years of follow‐up. The reduction was 34% for women aged 50‐74 years and 13% for women aged 40‐49 years. Results indicated that the reduced effect on mortality for women aged 40‐49 years was due to a differential effect of screening on the prognostic factors of tumor size, lymph node status, and histologic type. The mean sojourn times in the age groups 40‐49 years, 50‐59 years, 60‐69 years, and 70‐74 years were 1.7,3.3,3.8, and 2.6 years, respectively. Conclusions. These results suggest that much, a though not all, of the smaller effect of screening on mo tality in women aged 40‐49 years is due to faster progression of a substantial proportion of tumors in this age group and the rapid increase in incidence during this decade of life. It is concluded that the interval between screenings should be shortened to achieve a greater benefit in this age group. It is estimated that a 19% reduction in mortality would result from an annual screening regime.

The Swedish two county trial of breast cancer screening is now in its tenth year. This paper presents detailed results on mortality from breast cancer and from all other causes, and on the population denominators at risk for each of the first 8 years of follow up, for each county separately. These data represent a two year update on the last major report. Results show an increasingly significant deficit in deaths from breast cancer among the 77 092 women invited to screening relative to the 56 000 not invited (RR = 0-68, p = 0-002), with no significant difference between the effects of screening in the two counties (p = 0-5). These results remain the same when adjusted for age. Analysis of all cause deaths shows no significant effect of screening (p = 0 5), nor was there any significant effect of screening on deaths from all causes other than breast cancer (p = 0 9). The rates of deaths from intercurrent illness in breast cancer cases were almost identical in the group invited to screening and the group not invited (p = 0 7). This result remained the same when adjusted for age. We calculate that in the age group 50-69 at entry, one breast cancer death was prevented per 4000 woman/years, per 1460 mammographic examinations, per 13-5 biopsies, and per 7-4 breast cancers detected. The purpose ofthis paper is to present in fuller form the results on mortality, stressing the relationship of screening both to breast cancer and to total mortality. These results allow one to assess both the benefit of screening and the extent ofany possible adverse effects on mortality. In addition some questions about the value of breast cancer screening are addressed.Y9These include concern about the overall mortality rate among women invited to screening (with the related question of deaths from intercurrent illness among women who developed breast cancer), the reduction in mortality from breast cancer in age subgroups and the comparison of results in the two counties.The trial, as originally analysed, contained women who had previously had breast cancer among the population at risk (although not among the breast cancer cases or deaths as they were excluded at that stage). This imperfection has now been rectified and a definitive analysis is possible.Finally, it is possible that the slight difference in the age distributions of the study and control groups might have modifying effects on the results, since randomisation took place at the level of small communities in this trial. Although the age distributions of the study and control groups were closely similar, an analysis which takes into account the potential age affects, in addition to the updated information, is timely. MethodsThe design and management of the two county trial have been described elsewhere.' The numbers of individuals in the trial are shown tabulated by age and county in table 1. It is important to note that the control group is slightly younger than the group allocated to screening. Randomisation into the trial took place in the period 1977-80 and data a...

SummaryThe results of the Swedish two-county study are analysed with respect to tumour size, nodal status and malignancy grade, and the relationship of these prognostic factors to screening and to survival. It is shown that these factors can account for much of the differences in survival between incidence screen detected, interval and control group cancers but to a lesser extent for cancers detected at the prevalence screen where length bias is greatest. Furthermore, examination of the relationships among the prognostic factors and mode of detection indicates that malignancy grade, as a measure of inherent malignant capacity, evolves as a tumour grows. The proportion of cancers with poor malignancy grade is several fold lower for cancers of diameter less than 15 cm than for cancers greater than 30 cm, independent of the length bias of screening. The implications of these findings for screening frequency are briefly discussed.It has been shown that mortality from breast cancer can be reduced by mass screening using mammography (Shapiro et al., 1982;Tabar et al., 1985), a reduction resulting from earlier diagnosis. The natural history of breast cancer, however, is clearly heterogeneous, with substantial variation among tumours in their malignant potential, rate of growth and prognosis. Further, little is known of the rate at which prognosis deteriorates as a tumour develops or conversely how prognosis improves as the time of diagnosis is advanced.It is known that screening does reduce rates of larger tumours and of metastases Tabar et al., 1987). Moreover, these factors affect survival, as does malignancy grades. However, these relationships have not been fully quantified in a screening context, so the mechanism whereby screening can reduce mortality is not fully understood. The purpose of the present paper is to examine, using the results of the Swedish two-county study:(1) the relationships among the prognostic factors: tumour size, nodal involvement and malignancy grade; (2) the change in these factors brought about by screening; (3) the extent to which the change in the distributions of prognostic factors achieved by screening can account for the mortality reduction; (4) (Bloom & Richardson, 1957;Scarff & Torloni, 1968) was determined by one pathologist in each county, but as results demonstrate, there were differences between the two counties in proportions of grades 1, 2 and 3, probably reflecting subjectivity in classification of tumour grade rather than a difference in the two tumour populations. No such differences were observed between counties for tumour size or node status.Statistical analysis of associations among tumour characteristics was performed using log-linear modelling and logistic regression (Aitkin et al., 1989). These methods yield likelihood ratio (deviance) chi-squared tests for significance of associations and odds ratio estimates of relative risks (for example of being nodes positive for given grade relative to grade 1). Survival analysis was performed using proportional hazards regres...

Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282,777 women (156,911 invited and 125,866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relative risk estimates. All 1,296 deaths occurring in women with breast cancer detected after randomization were evaluated by an independent endpoint committee (EPC), consisting of four physicians who reviewed collected medical information that was blinded regarding mammography screening. If there was disagreement between the EPC members at the initial individual evaluation the final classification was made at consensus meetings. In only 6.9% (n = 89) of the cases was there disagreement as to whether breast cancer was or was not the underlying cause of death. It was also found that 'breast cancer as underlying cause of death' and 'breast cancer as underlying or contributory cause of death' according to Statistics Sweden resulted in relative risk estimates very similar to those based on the classification by the EPC. The study thus supports the use of official health statistics in the evaluation of randomized breast screening trials in Sweden.

o 1996 Wiky-Liss, Inc.

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The methods involving more explicit modelling of the disease process and fewer assumptions tended to find higher estimates of predictive value in the Two-County study. The results suggest that previously poor sensitivity and predictive value estimates may have been overpessimistic.