• Mike J Clarke.
• UK Cochrane Centre, National Institute for Health Research, Summertown Pavilion, Middle Way, Oxford, UK, OX2 7LG.
• Cochrane Db Syst Rev. 2008 Oct 8; 2008 (4): CD003647CD003647.

BackgroundThe long-term effects of radiotherapy on mortality from breast cancer and other causes remain uncertain.ObjectivesIn this report the Early Breast Cancer Trialists' Collaborative Group present their systematic overview of treatment with radiotherapy.Search StrategyTrial identification procedures for the EBCTCG overviews have been described elsewhere. See under "EBCTCG" in the Breast Cancer Group module.Selection CriteriaA meta-analysis was done of 10-year and 20-year results from 40 unconfounded randomised trials of radiotherapy for early breast cancer. Radiotherapy fields generally included not only chest wall (or breast) but also axillary, supraclavicular, and internal mammary nodes.Data Collection And AnalysisData collection involved central review of individual patient data on recurrence and cause-specific mortality from 20,000 women.Main ResultsA reduction of approximately two-thirds in local recurrence was seen in all trials, largely independent of the type of patient or type of radiotherapy (8.8% vs 27.2% local recurrence by year 10). Hence, to assess effects on breast cancer mortality of substantially better local control, results from all trials were combined. Breast cancer mortality was reduced (2p=0.0001) but other, particularly vascular, mortality was increased (2p=0.0003), and overall 20-year survival was 37.1% with radiotherapy versus 35.9% control (2p=0.06). There was little effect on early deaths, but logrank analyses of later deaths indicate that, on average after year 2, radiotherapy reduced annual mortality rates from breast cancer by 13.2% (SE 2.5) but increased those from other causes by 21.2% (SE 5.4). Nodal status, age, and decade of follow-up strongly affected the ratio of breast cancer mortality to other mortality, and hence affected the ratio of absolute benefit to absolute hazard from these proportional changes in mortality.Authors' ConclusionsRadiotherapy regimens able to produce the two-thirds reduction in local recurrence seen in these trials, but without long-term hazard, would be expected to produce an absolute increase in 20-year survival of about 2-4% (except for women at particularly low risk of local recurrence). The average hazard seen in these trials would, however, reduce this 20-year survival benefit in young women and reverse it in older women.

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