title: Does local recurrence affect the rate of distant metastases and survival in patients with early-stage breast carcinoma treated with breast-conserving therapy?
abstract: BACKGROUND
  The purpose of the current analysis was to evaluate the impact of local recurrence (LR) on the development of distant metastases (DM), overall survival (OS), and cause specific survival (CSS) in patients with early-stage breast carcinoma who underwent conservative surgery (CS) and received postoperative radiotherapy (RT).
  
  
  METHODS
  Between 1980 and 1995, 1169 patients underwent CS and received RT. All patients were followed for > 1 year and had < or = 4 lymph nodes involved with disease. The median duration of follow-up was 7.7 years. A Cox proportional hazards model was performed to evaluate the effect of LR on the development of DM and CSS. A matched-pair analysis that controlled for multiple prognostic factors also was performed comparing the outcomes of patients with and without LR.
  
  
  RESULTS
  The LR rate was 11% at 12 years. For the entire population, LR led to poorer OS and CSS rates at 12 years compared with local control (LC) (71% vs. 81% [P = 0.001] and 69% vs. 88% [P < 0.001], respectively). In a Cox multiple regression model, LR was a significant predictor of disease specific mortality. The hazard ratio (HR) associated with LR was 2.69 for mortality and 2.67 for DM (P < 0.001 and P < 0.001, respectively). The median time from surgery to the development of DM was 3.8 years for patients without LR compared with 4.7 years for patients with LR. Patients who developed LR also had two peaks in the rate of DM (at 2.5 years and at 6.5 years) compared to only one peak (at 1.5 years) for patients who did not develop LR. The impact of LR on DM still was evident in patients with small tumors (< or = 2.0 cm; P < 0.001), negative lymph nodes (P = 0.004), or both (P < 0.001). Recurrent disease that developed outside of the surgical bed region had no negative effect on survival. In the matched-pair analysis (controlling for age, tumor size, grade, number of positive lymph nodes, and estrogen receptor status), LR remained the most significant predictor of mortality (HR: mortality, 5.86; DM, 6.43).
  
  
  CONCLUSIONS
  The current results suggest that LR may be responsible for an increase in DM and disease specific mortality in patients who undergo CS and receive RT. This suggestion is reinforced by the distinct difference seen in the time distribution of DM after LR developed and by the fact that recurrent disease that originated outside of the surgical bed did not affect OS. These data reinforce the necessity to insure optimal LC in patients who are treated with breast-conserving therapy.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA. fvicini@beaumont.edu
authors.forename: Frank A
authors.initials: FA
authors.lastname: Vicini
authors.forename: Larry
authors.initials: L
authors.lastname: Kestin
authors.forename: Raywin
authors.initials: R
authors.lastname: Huang
authors.forename: Alvaro
authors.initials: A
authors.lastname: Martinez
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D012307:Risk Factors; D013997:Time Factors