title: Relationship between estrogen receptor, progesterone receptor, HER-2 and Ki67 expression and efficacy of aromatase inhibitors in advanced breast cancer.
abstract: BACKGROUND
  Surprisingly few data are published on the relevance of even commonly used biomarkers of response to aromatase inhibitors (AIs) in advanced breast cancer. Here, we aim to determine the effectiveness of AIs in that setting according to quantitative levels of estrogen receptor (ER), progesterone receptor (PgR) and Ki67 or human epithelial growth factor receptor-2 (HER-2) status.
  
  
  METHODS
  ER, PgR, HER-2 and Ki67 protein expressions were centrally assessed in 177 archival formalin-fixed paraffin-embedded primary or locally recurrent breast tumours from women who subsequently received AI treatment of advanced disease.
  
  
  RESULTS
  Among ER-positive patients (n = 146), higher PgR, but not ER, levels were associated with increased time to AI treatment failure (TTF). Higher Ki67 staining was associated with decreased TTF. ER-positive/HER-2-positive patients showed a non-significant trend for decreased TTF compared with ER-positive/HER-2-negative patients. PgR level, but not Ki67, remained a significant predictor of TTF in multivariate analysis of ER-positive patients.
  
  
  CONCLUSIONS
  Higher PgR and Ki67 levels are significantly associated with increased and decreased TTF, respectively, in ER-positive patients receiving AI treatment of advanced disease. The higher proliferation seen in PgR-negative tumours does not explain the poorer clinical responsiveness of this subgroup.
authors.affiliation: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK. helen.anderson@icr.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Hills
authors.forename: L
authors.initials: L
authors.lastname: Zabaglo
authors.forename: R
authors.initials: R
authors.lastname: A'hern
authors.forename: A F
authors.initials: AF
authors.lastname: Leary
authors.forename: B P
authors.initials: BP
authors.lastname: Haynes
authors.forename: I E
authors.initials: IE
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D017698:Postmenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D046888:Tissue Array Analysis; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D047072:Aromatase Inhibitors; D054316:Biomarkers, Pharmacological; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone