title: Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node-negative breast cancer patients.
abstract: OBJECTIVE
  To examine the importance of a fibrotic focus-a scar-like area in a carcinoma-as a marker of intratumoral hypoxia that correlates with angiogenesis and with clinical outcome in node-negative breast cancer.
  
  
  RESULTS
  One hundred and four T1-2N0M0 breast carcinoma patients were divided into two groups: group 1 (n=46) showing early distant relapse (median disease-free survival 25 months) and group 2 (n=58) showing no evidence of disease (median follow-up 91.5 months). All tumours were evaluated for medial/lateral location, size, histological grade, mitotic activity, necrosis, fibrotic focus, angiogenesis, vascular permeation and growth pattern. Multiple regression analysis showed that only histological grade and the presence of a fibrotic focus were independent predictors of early distant relapse. A fibrotic focus was present in 53% of the tumours. The relative size (fibrotic focus/tumour ratio) was significantly correlated with an unfavourable outcome. The presence of necrosis inside the fibrotic focus and the absolute and relative size of the fibrotic focus were significantly correlated with angiogenesis. A fibrotic focus was significantly associated with large, expansively growing tumours with high histological grade and numerous mitoses.
  
  
  CONCLUSIONS
  A fibrotic focus can be used as a surrogate for quantifying angiogenesis and is an independent predictor of early metastasis in lymph node-negative breast cancer.
authors.affiliation: Department of Pathology, University Hospital Antwerp, Belgium. Cecile.Colpaert@uza.be
authors.forename: C
authors.initials: C
authors.lastname: Colpaert
authors.forename: P
authors.initials: P
authors.lastname: Vermeulen
authors.forename: P
authors.initials: P
authors.lastname: van Beest
authors.forename: G
authors.initials: G
authors.lastname: Goovaerts
authors.forename: J
authors.initials: J
authors.lastname: Weyler
authors.forename: P
authors.initials: P
authors.lastname: Van Dam
authors.forename: L
authors.initials: L
authors.lastname: Dirix
authors.forename: E
authors.initials: E
authors.lastname: Van Marck
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009336:Necrosis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D013997:Time Factors