title: Influence of internal mammary node irradiation on long-term outcome and contralateral breast cancer incidence in node-negative breast cancer patients.
abstract: OBJECTIVE
  There is no general consensus concerning irradiation (RT) of internal mammary nodes (IMN) in axillary node-negative breast cancer. Based on a large series of patients treated in a single institute and followed up for a long period of time, we looked at the influence of IMN RT on late outcome of these patients as well as the development of contralateral breast cancer (CBC).
  
  
  METHODS
  The study was based on 1630 node-negative breast cancer patients treated in our institution between 1975 and 2008 with primary conservative surgery and axillary dissection or sentinel node examination. All patients received post-operative breast RT. IMN RT was more frequent in inner or central tumours. Kaplan-Meier (K-M) overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) according to IMN RT were calculated for all patients and for patients with inner/central tumours. The K-M rate of contralateral breast cancer (CBC) was also analysed and correlated with IMN RT.
  
  
  RESULTS
  Prognostic variables such as tumour size, histological grade, and hormone receptors were not significantly different in the groups having received IMN RT or not. Considering all patients, OS was strictly comparable in the 2 groups: 10-year values were 85% (IMN RT) and 86% (no IMN RT), respective values at 20 years were 66.6% and 61.0% (p=0.95). However, in patients presenting with inner/central tumours, OS was significantly improved in the IMN RT group with respective values of 92.5% and 87.2% at 10 years, and 80.2% and 63.3% at 20 years: Hazard ratio (HR)=0.56 (0.37-0.85); p=0.0052. Again, CSS was improved in patients with inner/central tumours having received IMN RT, with 20-year rates of 89.5% versus 79.1% in patients not receiving IMN RT (p=0.047). No difference in DFS was noticed. The actuarial rate of CBC development was comparable between patients having received IMN RT and other patients. However, considering only patients alive 10 years after primary breast surgery, the K-M rate of CBC at 20 years was 5.3% in patients without IMN RT and 7.2% in patients with such RT; HR=2.47 (1.23-4.95); p=0.008.
  
  
  CONCLUSIONS
  IMN RT in node-negative tumours was associated with increase in OS and CSS in patients with inner or centrally located lesions. An increase in CBC development was also noticed in long-survivors of IMN RT patients; however, these findings have to be interpreted with caution because of the difference in follow-up between the 2 groups. Further studies are warranted to investigate the potential role of IMN irradiation in the development of CBC.
authors.affiliation: Radiotherapy Department, Centre Antoine-Lacassagne, Nice, France. Electronic address: adel.courdi@nice.unicancer.fr.
authors.forename: Adel
authors.initials: A
authors.lastname: Courdi
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chamorey
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hannoun-Lévi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D015331:Cohort Studies; D015897:Comorbidity; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology* / Q000528:radiation effects / Q000601:surgery; D015182:Lymphatic Irradiation; D008207:Lymphatic Metastasis; D015412:Mastectomy, Segmental / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000473:pathology* / Q000628:therapy; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D020266:Radiotherapy, Conformal; D012189:Retrospective Studies; D018570:Risk Assessment; D021701:Sentinel Lymph Node Biopsy; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
keywords: Contralateral breast cancer; Inner tumours; Internal mammary nodes irradiation; Outcome; Survival