Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials
Darby S., McGale P., Correa C., Taylor C., Arriagada R., Clarke M., Cutter D., Davies C., Ewertz M., Godwin J., Gray R., Pierce L., Whelan T., Wang Y., Peto R.
BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35.0% to 19.3% (absolute reduction 15.7%, 95% CI 13.7-17.7, 2p<0.00001) and reduced the 15-year risk of breast cancer death from 25.2% to 21.4% (absolute reduction 3.8%, 1.6-6.0, 2p=0.00005). In women with pN0 disease (n=7287), radiotherapy reduced these risks from 31.0% to 15.6% (absolute recurrence reduction 15.4%, 13.2-17.6, 2p<0.00001) and from 20.5% to 17.2% (absolute mortality reduction 3.3%, 0.8-5.8, 2p=0.005), respectively. In these women with pN0 disease, the absolute recurrence reduction varied according to age, grade, oestrogen-receptor status, tamoxifen use, and extent of surgery, and these characteristics were used to predict large (>/=20%), intermediate (10-19%), or lower (<10%) absolute reductions in the 10-year recurrence risk. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories were 7.8% (95% CI 3.1-12.5), 1.1% (-2.0 to 4.2), and 0.1% (-7.5 to 7.7) respectively (trend in absolute mortality reduction 2p=0.03). In the few women with pN+ disease (n=1050), radiotherapy reduced the 10-year recurrence risk from 63.7% to 42.5% (absolute reduction 21.2%, 95% CI 14.5-27.9, 2p<0.00001) and the 15-year risk of breast cancer death from 51.3% to 42.8% (absolute reduction 8.5%, 1.8-15.2, 2p=0.01). Overall, about one breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, and the mortality reduction did not differ significantly from this overall relationship in any of the three prediction categories for pN0 disease or for pN+ disease. INTERPRETATION: After breast-conserving surgery, radiotherapy to the conserved breast halves the rate at which the disease recurs and reduces the breast cancer death rate by about a sixth. These proportional benefits vary little between different groups of women. By contrast, the absolute benefits from radiotherapy vary substantially according to the characteristics of the patient and they can be predicted at the time when treatment decisions need to be made. FUNDING: Cancer Research UK, British Heart Foundation, and UK Medical Research Council.