No Mortality Benefit of Mammography Screening in 25-Year Follow-up of Canadian National Breast Screening Study
As reported in BMJ by Miller et al, the 25-year follow-up of the Canadian National Breast Screening Study has shown no mortality benefit of annual mammography screening for breast cancer compared with physical examination or usual care. Mammography screening was associated with substantial overdiagnosis.
Study Details
In the study, 89,835 women aged 40 to 59 years from 15 screening centers in six Canadian provinces were randomly assigned to five annual mammography screens (n = 44,925) or no mammography (n = 44,910) during 1980 to 1985. Women aged 40 to 49 years in the mammography group and women aged 50 to 59 years in both groups received annual physical breast examinations, and women aged 40 to 49 years in the control group received a single breast examination followed by usual care in the community. The main outcome measure was deaths from breast cancer.
Incidence
The subjects were followed for incident breast cancer for up to 25 years (mean, 21.9 years). During the 5-year screening period, 666 invasive cancers were diagnosed in the mammography group and 524 were diagnosed in the control group. An additional 2,584 and 2,609 cancers were diagnosed during further follow-up. Of the 666 cancers detected in the mammography group during the screening period, 484 (73%) were screen-detected, 176 (27%) were interval cancers (detected within 1 year of last screening), and data were missing for 6.
During the screening period, the mean sizes of the diagnosed cancers were 1.91 cm in the mammography group and 2.10 cm (P = .01) in the control group; 30.6% vs 32.4% were node-positive (P = .053), and 68.2% vs 100% were palpable. Palpable cancers had larger average size than cancers detected only on mammography (2.1 vs 1.4 cm, P < .001) and were more likely to be node-positive (34.7% vs 16.5%, P < .001).
The investigators noted, “Annual mammography screening detected a significant number of small non-palpable breast cancers, but half of these were examples of over-diagnosis.”
Survival by Characteristics
A total of 1,005 women (1.1% of total population) died from breast cancer during the 25-year follow-up, including 351 (29%) of 1,190 who were diagnosed during the screening period. The 25-year survival was 70.6% for women with breast cancer detected in the mammography group and 62.8% for those with cancers diagnosed in the control group (hazard ratio [HR] = 0.79, P = .02).
The authors noted, “Although the difference in survival after a diagnosis of breast cancer was significant between those cancers diagnosed by mammography alone and those diagnosed by physical examination screening, this is due to lead time, length time bias, and over-diagnosis.”
Survival rates for women with palpable cancer were similar in the two groups (66.3% vs 62.8%), and the survival rate for women with cancer diagnosed by mammography only (nonpalpable) was 79.6%. In the mammography group, women with nonpalpable cancer had significantly longer survival than those with palpable cancer (HR = 0.58, P < 10-4), and those with screen-detected cancer had longer survival vs those with interval cancer (HR = 0.61, P = .001).
Breast Cancer and Overall Mortality
Of the 666 women (of 44,925) in the mammography group and 524 (of 44,910) in the control group diagnosed with cancer during the 5-year screening period, 180 and 171 patients, respectively, died from breast cancer during the 25-year follow-up.
The overall hazard ratio for death from breast cancer diagnosed during the screening period was 1.05 (95% confidence interval [CI] = 0.85–1.30, P = .63). The hazard ratio remained similar if the screening period was extended to 6 years (1.06, P = .55) or 7 years (1.07, P = .46). Findings were similar among women aged 40 to 49 years (HR = 1.09, P = .58) and among women aged 50 to 59 years (HR = 1.02, P = .88).
Over total follow-up, 3,250 women in the mammography arm and 3,133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. There was no significant difference between groups in 25-year cumulative mortality from breast cancer (HR = 0.99, 95% CI = 0.88–1.12, P = .87).
A total of 9,477 women (10.6%) died during the follow-up period. There was no significant difference between the mammography group and the control group in 25-year cumulative mortality from all causes (HR = 1.02, 95% CI = 0.98–1.06, P = .28).
Overdiagnosis
By the end of the 5-year screening period, there were 142 excess cases of breast cancer in the mammography group (666 vs 524). At 15 years after enrollment, the excess number of cancers in the mammography group became constant at 106 cancers. The excess number represents 22% (106/484) of all screen-detected cancers. Thus, there was one case of overdiagnosis of breast cancer for every 424 women screened by mammography during the trial.
The investigators concluded, “[O]ur data show that annual mammography does not result in a reduction in breast cancer specific mortality for women aged 40 to 59 beyond that of physical examination alone or usual care in the community. The data suggest that the value of mammography screening should be reassessed.”
They further noted, “[I]n technically advanced countries, our results support the views of some commentators that the rationale for screening by mammography should be urgently reassessed by policy makers. Nevertheless, education, early diagnosis, and excellent clinical care should continue to be provided to women to ensure that as many breast tumours as possible are diagnosed at or less than 2 cm.”
Anthony B. Miller, MD, of the University of Toronto, is the corresponding author for the BMJ article.
The study was supported by the Canadian Breast Cancer Research Alliance, Canadian Breast Cancer Research Initiative, Canadian Cancer Society, Health and Welfare Canada, National Cancer Institute of Canada, Alberta Heritage Fund for Cancer Research, Manitoba Health Services Commission, Medical Research Council of Canada, le Ministère de la Santé et des Services Soçiaux du Québec, Nova Scotia Department of Health, and Ontario Ministry of Health. The study authors reported no potential conflicts of interest.
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