title: Adjuvant radiation therapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials- an update.
abstract: BACKGROUND
  Adjuvant radiotherapy (RT) of regional lymph nodes (LN) in early breast cancer is still a matter of debate. RT increases the Overall survival (OS) rate of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved LN. The contribution of RT to regional LN to this improvement was poorly identified. Recently, the results of three large randomized trials addressing this question were published as full papers.
  
  
  METHODS
  Published data of the MA.20 (n = 1832), the EORTC22922-10925 (EORTC) (n = 4004) trial and the French trial (n = 1334) were the foundation of this meta-analysis. Major eligibility criteria were positive i) axillary LN (all trials), ii) LN negative disease with high risk for recurrence (MA.20), and iii) medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial analyzed the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS).
  
  
  RESULTS
  Regional RT of MS-LN and IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS [Hazard Ratio (HR) 0.88 (95 % CL 0.78 - 0.99)]. Adding results of the French trial and using a random effects model to respect the different design of the French trial, the effect on OS of regional RT remained significant [HR 0.90 (95 % CL 0.82 - 0.99)]. The absolute benefits in OS were 1 % in the MA.20 trial at 10 years, 1.6 % in the EORTC trial at 10 years, and 3.3 % in the French trial at 10 years (not significant in single trials). Regional RT of MS-LN and IM-LN (MA.20 and EORTC) yielded to a significant improvement of DFS [HR 0.86 (95 % CL 0.78 - 0.95)] and DMFS [HR 0.84 (95 % CL 0.75 - 0.94)].
  
  
  CONCLUSIONS
  Additional regional RT to the internal mammary and medial supraclavicular LN statistically significantly improved DFS, DMFS, and OS in stage I-III breast cancer.
authors.affiliation: Department of Radiation Oncology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany. wilfried.budach@med.uni-duesseldorf.de.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Budach
authors.affiliation: Department of Radiation Oncology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany. Boelke@med.uni-duesseldorf.de.
authors.forename: Edwin
authors.initials: E
authors.lastname: Bölke
authors.affiliation: Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. kkammers@jhsph.edu.
authors.forename: Kai
authors.initials: K
authors.lastname: Kammers
authors.affiliation: Department of Dermatology, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany. PeterArne.Gerber@med.uni-duesseldorf.de.
authors.forename: Peter Arne
authors.initials: PA
authors.lastname: Gerber
authors.affiliation: Department of Senology, Sana Krankenhaus Gerresheim, Dusseldorf, Germany. dr.nestle-kraemling@t-online.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Nestle-Krämling
authors.affiliation: Department of Radiation Oncology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany. matuschek@med.uni-duesseldorf.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Matuschek
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D016032:Randomized Controlled Trials as Topic