title: DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer.
abstract: OBJECTIVE
  It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early-stage node-positive breast cancer.
  
  
  METHODS
  In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat.
  
  
  RESULTS
  A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease.
  
  
  CONCLUSIONS
  In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer.
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany. liseb@oncology.au.dk.
authors.forename: Lise Bech Jellesmark
authors.initials: LB
authors.lastname: Thorsen
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Birgitte Vrou
authors.initials: BV
authors.lastname: Offersen
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Hella
authors.initials: H
authors.lastname: Danø
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Berg
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Ingelise
authors.initials: I
authors.lastname: Jensen
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Anders Navrsted
authors.initials: AN
authors.lastname: Pedersen
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Sune Jürg
authors.initials: SJ
authors.lastname: Zimmermann
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Brodersen
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Overgaard
authors.affiliation: Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune Jürg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-Jürgen Brodersen, St Franziskus-Hospital, Flensburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000528:radiation effects*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant