Update of the Swedish Two-County Trial of breast cancer screening: histologic grade-specific and age-specific results

Abstract

The benefit of mammographic screening in reducing mortality from breast cancer is well established. Questions remain with respect to the magnitude of the long-term benefit of modern mammography screening, age specific benefits and the timing of these, and histology specific effects.

Methods: The Swedish Two-County Trial was set up in 1977, with 77,080 women aged 40-74 randomised to invitation to mammographic screening for breast cancer (active study population, ASP) and 55,985 women randomised to no invitation (passive study population, PSP). There is now follow-up for mortality to 31 December 1996, approximately 18 years average follow-up. We investigated the effect of invitation of screening on breast cancer mortality and incidence of advanced tumours by age group (40-49 and 50-74) and histologic type. In addition we estimated progression rates by histologic grade using markov chain models.

Results: A significant 29% reduction in breast cancer mortality was observed in association with invitation to screening (relative risk = 0.71, 95% confidence interval 0.60-0.83), maintaining the effect observed at previous stages of follow-up. Age-specific analyses show a smaller and later mortality benefit in women aged 40-49. This is related to the fact that there is a considerable benefit from early detection in terms of mortality from aggressive, poorly differentiated cancers in women aged 50-74, whereas the major effect in women aged 40-49 is on the less aggressive tumours of good or intermediate differentiation. Among women aged 50-74, the incidence of grade III tumours in the ASP is significantly lower than in the PSP, but this is not the case for women aged 40-49. This is related to the greater prevalence and rapidity of progression with respect to histologic grade, as evidenced by the results of markov chain models and the proportions of grade III tumours by time since last screen.

Conclusions: The substantial and significant mortality benefit of invitation to mammographic screening in women aged 40-74 is maintained at 18 years of follow-up. To achieve a substantial mortality benefit at an early stage in the screening program in women aged under 50 years, an interscreening interval of 12-18 months would be required.