title: Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials.
abstract: BACKGROUND
  Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.
  
  
  METHODS
  We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.
  
  
  RESULTS
  3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·68, 95% CI 0·57-0·82, 2p=0·00006), and breast cancer mortality (RR 0·80, 95% CI 0·67-0·95, 2p=0·01). 1133 of these 1314 women were in trials in which systemic therapy (cyclophosphamide, methotrexate, and fluorouracil, or tamoxifen) was given in both trial groups and, for them, radiotherapy again reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·67, 95% CI 0·55-0·82, 2p=0·00009), and breast cancer mortality (RR 0·78, 95% CI 0·64-0·94, 2p=0·01). For 1772 women with axillary dissection and four or more positive nodes, radiotherapy reduced locoregional recurrence (2p<0·00001), overall recurrence (RR 0·79, 95% CI 0·69-0·90, 2p=0·0003), and breast cancer mortality (RR 0·87, 95% CI 0·77-0·99, 2p=0·04).
  
  
  CONCLUSIONS
  After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.
  
  
  BACKGROUND
  Cancer Research UK, British Heart Foundation, UK Medical Research Council.
authors.forename: P
authors.initials: P
authors.lastname: McGale
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: C
authors.initials: C
authors.lastname: Correa
authors.forename: D
authors.initials: D
authors.lastname: Cutter
authors.forename: F
authors.initials: F
authors.lastname: Duane
authors.forename: M
authors.initials: M
authors.lastname: Ewertz
authors.forename: R
authors.initials: R
authors.lastname: Gray
authors.forename: G
authors.initials: G
authors.lastname: Mannu
authors.forename: R
authors.initials: R
authors.lastname: Peto
authors.forename: T
authors.initials: T
authors.lastname: Whelan
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Darby
mesh_terms: D001365:Axilla; D001943:Breast Neoplasms / Q000401:mortality* / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008408:Mastectomy; D009364:Neoplasm Recurrence, Local; D016032:Randomized Controlled Trials as Topic