Background: The long-term effects of radiotherapy on mortality from breast cancer and other causes remain uncertain.
Methods: A meta-analysis was done of 10-year and 20-year results from 40 unconfounded randomised trials of radiotherapy for early breast cancer. It involved central review of individual patients' data on recurrence and cause-specific mortality from 20000 women, half with "node-positive" disease. Radiotherapy fields generally included not only chest wall (or breast) but also axillary, supraclavicular, and internal mammary nodes.
Findings: A 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.
Interpretation: Radiotherapy 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.