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

Abstract

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.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Figures

Figure 1

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 10-year risk of any (locoregional or distant) first recurrence and on 15-year risks of breast cancer death and death from any cause in 10 801 women (67% with pathologically node-negative disease) in 17 trials Further details are in webappendix p 5. RR=rate ratio. Rate ratios in this figure include all available years of follow-up.

Figure 2

Effect of radiotherapy (RT) after breast-conserving surgery (BCS) on 10-year risk of any (locoregional or distant) first recurrence and on 15-year risk of breast cancer death in women with pathologically verified nodal status Vertical lines indicate 1 SE above or below the 5, 10, and 15 year percentages. Further details are in webappendix pp 6–7. pN0=pathologically node-negative. pN+=pathologically node-positive. RR=rate ratio. Rate ratios in this figure include all available years of follow-up.

Figure 3

Event rates for any (locoregional or distant) first recurrence (% per year) and recurrence rate ratios for various factors, considered separately, during years 0–9 in women with pathologically node-negative disease (n=7287) BCS=breast-conserving surgery. RT=radiotherapy. ER=oestrogen receptor. Categories including unknowns excluded from tests for trend and heterogeneity. †A trial policy of tamoxifen use gives tamoxifen to both treatment groups if the disease is ER positive (or ER unknown, here counted with ER positive); additional therapy could be chemotherapy (usually cyclophosphamide, methotrexate, fluorouracil [CMF]) for both treatment groups, or additional RT (nodal RT or a boost or both) for those allocated BCS+RT. ‡Definitions of trial categories A, B, and C are in table 1. Further details are in webappendix p 14.

Figure 4

Absolute 10-year risks (%) of any (locoregional or distant) first recurrence with and without radiotherapy (RT) following breast-conserving surgery (BCS) in pathologically node-negative women by patient and trial characteristics, as estimated by regression modelling of data for 7287 women Further details are in webappendix pp 27–30. Results for 5-year risks are in webappendix pp 31–34. Bars show 10-year risks in women allocated to BCS only, dark sections show 10-year risks in women allocated to BCS plus RT, light sections show absolute reduction with RT. ER=oestrogen receptor.

Figure 5

Absolute reduction in 15-year risk of breast cancer death with radiotherapy (RT) after breast-conserving surgery versus absolute reduction in 10-year risk of any (locoregional or distant) recurrence Women with pN0 disease are subdivided by the predicted absolute reduction in 10-year risk of any recurrence suggested by regression modelling (pN0-large ≥20%, pN0-intermediate 10–19%, pN0-lower