Randomization: Individual, but with significant imbalances in the distribution of women between assigned arms, as evidenced by menopausal status (P < .0001) and education (P = .05).
Sample size: 30,000 to 31,092 in study group and 30,565 to 30,765 in control group.
Consistency of reports: Variation in sample size reports.
Intervention: Annual two-view mammography (MMG) and CBE for 3 years.
Control: Usual care.
Compliance: Nonattenders to first screening (35% of the screened population) were not reinvited.
Contamination: Screening MMG was not available outside the trial, but frequency of CBE performance among control women is unknown.
Cause of death attribution: Women who died of breast cancer that had been diagnosed before entry into the study were excluded from the comparison between the screening and control groups. However, these exclusions were determined differently within the two groups. Women in the screening group were excluded based on determinations made during the study period at their initial screening visits. These women were dropped from all further consideration in the study. By design, controls did not have regular clinic visits, so the prestudy cancer status of control patients was not determined. When a control patient died and her cause of death was determined to be breast cancer, a retrospective examination was made to determine the date of diagnosis of her disease. If this was prior to the study period then she was excluded from the analysis. This difference in methodology has the potential for a substantial bias in comparing breast cancer mortality between the two groups, and this bias is likely to favor screening.
External audit: No.
Follow-up duration: 18 years.
Relative risk of breast cancer death, screening versus control (95% confidence interval [CI]): 0.71 (0.55–0.93) at 10 years and 0.77 (0.61–0.97) at 15 years.
Comments: The MMGs were of poor quality compared with those of later trials, because of outdated equipment and techniques. One should remember that the intervention consisted of both MMG and CBE. Major concerns about trial performance are the validity of the initial randomization and the differential exclusion of women with a prior history of breast cancer.
Randomization: Individual, within each birth year cohort for the first phase, MMG screening trial (MMST I). Individual for the entire birth cohort 1933 to 1945 for MMST II, but with variations imposed by limited resources. Validation by analysis of age in both groups shows no significant difference.
Exclusions: In a Swedish meta-analysis, there were 393 women with pre-existing breast cancer excluded from the intervention group, and 412 from the control group. Overall however, there were 86 more women excluded from the intervention group than from the control group.
Sample size: 21,088 study and 21,195 control.
Consistency of reports: No variation in patient numbers.
Intervention: Two-view MMG every 18 to 24 months × 5.
Control: Usual care, with MMG at study end.
Compliance: Participants migrating from Malmo (2% per year) were not followed. The participation rate of study women was 74% for the first round and 70% for subsequent rounds.
Contamination: 24% of all control women had at least one MMG, as did 35% of the control women aged 45 to 49 years.
Cause of death attribution: 76% autopsy rate in early report, lower rate later. Cause of death assessment blinded for women with a breast cancer diagnosis. Linked to Swedish Cause of Death Registry.
Analysis: Evaluation, initially. Follow-up analysis, as part of the Swedish meta-analysis.
External audit: No.
Follow-up duration: 12 years.
Relative risk of breast cancer death, screening versus control (95% CI): 0.81 (0.62–1.07).
Comments: Evaluation analysis required a correction factor for the delay in the performance of MMG in the control group. The two Malmo trials MMST I and MMST II have been combined for most analyses.