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

Abstract

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. ConclusionAnnual 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.

DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood

“…In addition, a recent 25-year follow-up study for BC even questioned the benefit of mammography to women in general. 50 The blood-based HYAL2 methylation can objectively detect BC at very early stage (stages 0 and I, AUC 5 0.89, sensitivity: 64.4%, specificity: 90%, Fig. 5d), and is efficient for women under 50 years as well (age < 50 years, AUC 5 0.87, sensitivity: 62.1%, specificity: 90%, Fig.…”

Medical Debates and Medical Reversal

“…Mammography is also associated with false-positive test results that cause real harm via anxiety and overdiagnosis. 5 Those who argue that a recent negative mammography trial 6 should put an end to the use of mammogram-based breast cancer screening contend that the randomized controlled trial is our best source of data. These Bminimalists^cite the evidence of harm (overdiagnosis and overtreatment).…”

Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast‐screening

“…The effects of CBE with and without mammography on downstaging have been the subject of a few RCT where downstaging of disease has been observed, but insufficient follow‐up had elapsed to observe differences in mortality between arms 28, 29. Furthermore, the 25‐year follow‐up of the Canadian National Breast Screening Study found that annual mammography in women aged 40–59 had no additional benefit beyond that of CBE in terms of mortality 30. The inclusion of CBE in the Colombian guidelines was intended to increase detection rates and reduce the chance of interval cancers.…”