Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.

OBJECTIVE: To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening.

DESIGN: Follow-up of randomised screening trial by centre coordinators, the study's central office, and linkage to cancer registries and vital statistics databases.

SETTING: 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia).

PARTICIPANTS: 89,835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography).

INTERVENTIONS: Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community.

MAIN OUTCOME MEASURE: Deaths from breast cancer.

RESULTS: During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44,925 participants) and 524 in the controls (n=44,910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis.

CONCLUSION: Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.