Breast screening, prognostic factors and survival – results from the Swedish two county study

Abstract

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...

Population estimates of survival in women with screen-detected and symptomatic breast cancer taking account of lead time and length bias

“…Uncorrected comparisons of screen-detected with symptomatic cancers in other breast cancer populations yield similar results to our uncorrected analysis [2][3][4]. This suggests that our bias-corrected estimates are also generalisable.…”

“…It has been observed, both in the trials and the screening programmes, that survival is much better in women with screen-detected cancers than in those with tumours detected symptomatically [2][3][4]. The survival of women with screen-detected breast cancers, however, is known to be inflated by both lead time and length bias [5].…”

Declining mortality from breast cancer in Yorkshire, 1983–1998: extent and causes

“…Partial TNM information was available for an additional 8912 (27%) cases, which were classified into two intermediate groups, one (termed I/II) including any tumours with size T1 and the other (termed II/III) including any tumours with size T2 or larger; both these groups excluded cases with evidence of metastases. Owing to the high correlation between tumour size and other parameters of stage (Duffy et al, 1991;Crisp et al, 1993), it was assumed that most cases in group I/II were either stage I or II and that group II/III included mainly stages II and III. The residual proportion of cases with no or insufficient information on stage was 48%.…”

Specialisation and breast cancer survival in the screening era

“…Lengthtime bias was a possible confounding factor as screening may preferentially detect slower growing, more favourable tumours (Duffy et al, 1991;Klemi et al, 1992). This was confirmed, as the method of detection remained a highly significant variable in the survival analysis after allowing for all other factors (RHR ¼ 0.59, Po0.001).…”