THE SWEDISH TWO-COUNTY TRIAL TWENTY YEARS LATER: Updated Mortality Results and New Insights from Long-Term Follow-up

doi:10.1016/S0033-8389(05)70191-3

Radiologic Clinics of North America

Volume 38, Issue 4, 1 July 2000, Pages 625-651

https://doi.org/10.1016/S0033-8389(05)70191-3 Get rights and content

The Swedish Two-County Trial is a randomized controlled trial of invitation to breast cancer screening. It was initiated in late 1977, with 133,000 women randomized between 1977 and 1979 to regular invitation to screening or to no invitation. The first mortality results were published in 1985, showing a significant 30% reduction in breast cancer mortality associated with invitation to screening.¹⁰ On establishment of the benefit in mortality, the control group was invited to screening. On further regular follow-up, the mortality benefit has consistently remained around 30%.⁶

At around 11 years' follow-up, an update of results and a detailed investigation of the screening practice and its impact on the tumor population was published in this journal.⁹ This research established the continued mortality benefit and showed that screening achieved this benefit by diagnosing high-risk tumors at an earlier stage and particularly while they are small. We now have follow-up to the end of 1998, so at approximately the twentieth anniversary of the trial it is appropriate to update the results further and establish what can be learned from long-term follow-up, notably of the tumor population diagnosed in this trial.

Section snippets

DESIGN AND METHODS

The design of the Two-County study has been described repeatedly in previous publications.6, 8, 9, 10 The trial was a cluster-randomized controlled trial taking place in two counties in Sweden, Kopparberg (W-county), now called Dalarna, and Östergötland (E-county). The trial randomized 77,080 women aged 40 to 74 years to invitation to screening (active study population [ASP]), and 55,985 to no invitation (passive study population [PSP]). Screening began in the ASP in 1977. On establishment of a

RESULTS: MORTALITY AND SCREENING PERFORMANCE

Figure 1 shows the breast cancer mortality in the ASP and PSP. At 20 years follow-up, there is a significant 32% reduction in mortality associated with invitation to screening (relative risk [RR]=0.68, 95% confidence interval [CI] 0.59 to 0.80, P<0.001). The corresponding numbers of cancers, deaths, and person-years are given in Table 1. Figure 2 shows the cumulative mortality further stratified by age group and county. The largest effect on mortality can be seen at ages 50 to 69. Results for

RESULTS: SCREENING, HISTOLOGY, AND PROGNOSIS

Figures 3 to 10 show survival by histologic type, size, and node status. Figure 11 shows survival by size in those of any histologic type that did not receive axillary dissection. From this, one can categorize tumors for each histologic type as having good, intermediate, and poor prognosis. These are summarized in Table 4. Figure 12 shows the survival over time by prognostic group for all histologic types combined. Clearly, the goal of screening is to shift the balance of the distribution from

RESULTS: MAMMOGRAPHIC FINDINGS AND PROGNOSIS OF SMALL TUMORS

The criteria shown in Table 4 illustrate the importance of tumor size for survival. Figure 17 shows survival by tumor size in the invasive tumors in our population. The effect of size on survival is very strong, as one expects with increasingly poor survival with increasing size. From Figures 4 to 6 it can be seen that this dependence of survival on size is particularly strong for ductal carcinoma. Despite the high survival rates among small tumors, there are still some tumors of size 1 to 9 mm

RESULTS: DIAGNOSIS AND DISCRIMINATION OF SMALL BUT HIGH-RISK TUMORS

Mammography is clearly a very useful tool, not only for early detection of cancers but also for successful discrimination between the highly fatal and nonfatal cancers. The four mammographic prognostic features are (Figs. 20 to 23):

1
Spiculated tumor mass with no associated calcifications.
2
Circular- or oval-shaped tumor mass with no associated calcifications.
3
Spiculated or circular- or oval-shaped tumor mass, associated with either pleomorphic-heterogeneous-granular–type or

Updated Mortality Results and Screening Measures

Our results show a 32% reduction in breast cancer mortality that is maintained 20 years after randomization and around 13 years after the end of the screening phase of the trial. That is, the ASP continues to have lower mortality from breast cancer than the PSP despite the fact that for the last 13 years there has been no difference in intervention applied to the two groups. Considered another way, screening in 1977 to 1985 was continuing to save lives in 1998. The absolute costs have remained

SUMMARY

The benefit of invitation to mammographic screening observed in this trial is maintained as a highly significant 32% reduction in breast cancer mortality. Mammographic screening for breast cancer continues to save lives after up to 20 years. Screening derives this benefit by improving the distribution of tumors diagnosed with respect to prognostic categories based on node status, size, and histology of tumors. There is potential for modern screening programs with shorter interscreening

ACKNOWLEDGMENTS

We thank the American Cancer Society and the Swedish Cancer Society for financial assistance with this research.

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: Address reprint requests to László Tabár, MD, Mammagraphy Department, Central Hospital, S-79182, Falun, Sweden

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THE SWEDISH TWO-COUNTY TRIAL TWENTY YEARS LATER: Updated Mortality Results and New Insights from Long-Term Follow-up

Section snippets

DESIGN AND METHODS

RESULTS: MORTALITY AND SCREENING PERFORMANCE

RESULTS: SCREENING, HISTOLOGY, AND PROGNOSIS

RESULTS: MAMMOGRAPHIC FINDINGS AND PROGNOSIS OF SMALL TUMORS

RESULTS: DIAGNOSIS AND DISCRIMINATION OF SMALL BUT HIGH-RISK TUMORS

Updated Mortality Results and Screening Measures

SUMMARY

ACKNOWLEDGMENTS

Radiol Clin North Am

Lancet

Lancet

Mammography: A contrary view

Ann Intern Med

Statistical Methods in Cancer Research II: The Design and Analysis of Cohort Studies