title: The prognostic significance of lymphovascular invasion in invasive breast carcinoma.
abstract: BACKGROUND
  Although lymphovascular invasion (LVI) has been associated with a poor outcome in patients with breast cancer, it is not included in most internationally recognized staging systems, including the American Joint Committee on Cancer tumor, lymph node, metastasis (TNM) classification. This is mainly because it remains unclear whether the presence of LVI is an independent, high-risk criterion in clinically relevant staging subgroups.
  
  
  METHODS
  The current study was based on a large and well characterized consecutive series of patients who had operable (pathologic T1 [pT1]-pT2, pathologic N0 [pN0]-pN3, M0) breast cancer (3812 informative cases) who were treated according to standard protocols at a single institution and who had long-term follow-up to assess the prognostic value of definite LVI in clinically and molecularly relevant staging subgroups.
  
  
  RESULTS
  LVI was strongly associated with both breast cancer-specific survival (BCSS) and distant metastasis-free survival (DMFS) in the entire series and in different subgroups. Multivariate analyses identified LVI as an independent predictor of both BCSS and DMFS in patients with operable breast cancer overall; in the TNM clinical subgroups pT1a-pT1c/pN0 and pT2/pN0; and in the molecular classes estrogen receptor (ER)-positive, ER-negative, human epidermal growth factor 2 [HER2]-negative, and triple-negative. In patients who had lymph node-negative tumors, LVI could be used as a high-risk criterion providing survival disadvantage equivalent to that provided by 1 or 2 involved lymph nodes (pN0 to pN1) and to that provided by 1 size category (pT1 to pT2). The use of immunohistochemistry for detecting an endothelial-specific marker contributed to the prognostic significance of LVI when applied to routine LVI negative/possible cases.
  
  
  CONCLUSIONS
  LVI provided a strong predictor of outcome in patients with invasive breast cancer and should be incorporated into breast cancer staging systems.
authors.affiliation: Department of Histopathology, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom. emadrakha@yahoo.com
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.forename: Stewart
authors.initials: S
authors.lastname: Martin
authors.forename: Andrew H S
authors.initials: AH
authors.lastname: Lee
authors.forename: David
authors.initials: D
authors.lastname: Morgan
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Hodi
authors.forename: Douglas
authors.initials: D
authors.lastname: Macmillan
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D019043:Vascular Neoplasms / Q000556:secondary*