title: Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10 years in early stage breast cancer.
abstract: BACKGROUND
  Locoregional recurrence (LRR) after breast-conserving therapy is a well-known independent risk factor associated with unfavourable long-term outcome. Controversy exists concerning the prognostic impact of a LRR after a very long event-free interval.
  
  
  METHODS
  Patients who underwent breast-conserving therapy for early stage breast cancer were pooled from four European Organisation for Research and Treatment of Cancer (EORTC) Breast Group trials. Only LRR as a first event was taken into account. Risk factors such as tumour size, nodal status, young age and chemotherapy were assessed in multivariate Cox regression analysis. LRR was used as a time-dependent variable in the landmark analysis for distant disease-free survival (DFS) and overall survival (OS). Patients were categorised as having at least 0, 5 or 10 years event-free survival.
  
  
  RESULTS
  In total, 7751 early stage breast cancer patients were included with a median follow-up of 10.9 years. Tumour size, nodal status, young age and chemotherapy are strong independent prognostic factors with a significant impact on long-term outcome, but lose their power and significance over time. Including all patients, LRR was the strongest prognostic factor for OS and distant DFS (resp. HR 5.01 and HR 5.31, p<0.001). In the subgroup of patients developing a LRR after at least 5 or 10 years, LRR remained the strongest independent prognostic factor for OS (resp. HR 3.98, HR 4.96, p ≤ 0.001) and distant DFS (HR 4.42, HR 7.57 p<0.001).
  
  
  CONCLUSIONS
  This is the first study which shows LRR after breast-conserving therapy is a very strong, time-independent prognostic factor for long term outcome in early stage breast cancer patients. These findings suggest that a LRR after a long event-free interval seems to be an indicator rather than an instigator of subsequent distant disease.
authors.affiliation: Department of Surgery, The Netherlands Cancer Institute, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Tanis
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: H
authors.initials: H
authors.lastname: Bartelink
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.forename: J A
authors.initials: JA
authors.lastname: van der Hage
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors