title: Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer.
abstract: BACKGROUND
  The role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-1s association with Ki67 and ER/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) profiles.
  
  
  METHODS
  TIMP-1 expression was evaluated by immunohistochemistry (IHC) on formalin fixed paraffin embedded primary tumor tissue in two independent cohorts comprised of 236 and 192 patients, respectively.
  
  
  RESULTS
  No differences in disease free survival (HR 0.98; 95% CI 0.63-1.53; p = 0.92) and overall survival (HR 0.94; 95% CI 0.63-1.43; p = 0.79) were observed according to TIMP-1 status. A significant negative association between TIMP-1 and Ki67 was identified (p = 0.015). TIMP-1 expression did not differ significantly according to ER/PR/HER2 profiles. When analyzed as separate variables PR and HER2 status tended to have a positive but non-significant association with TIMP-1 (PR: p = 0.08; OR 2.54; 95% CI 0.91-7.10, HER2: p = 0.08; OR 0.48; 95% CI 0.21-1.08) whereas ER status was not associated with TIMP-1 expression (p = 0.48; OR 0.68; 95% CI 0.23-1.99).
  
  
  CONCLUSIONS
  TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen. We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1 and PR.
authors.affiliation: Sino-Danish Breast Cancer Research Centre at Section of Pathobiology, Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. chab@life.ku.dk
authors.forename: Christina
authors.initials: C
authors.lastname: Bjerre
authors.forename: Ann
authors.initials: A
authors.lastname: Knoop
authors.forename: Karsten
authors.initials: K
authors.lastname: Bjerre
authors.forename: Mathilde S
authors.initials: MS
authors.lastname: Larsen
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Henriksen
authors.forename: Maria B
authors.initials: MB
authors.lastname: Lyng
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Ditzel
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Rasmussen
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Anne-Vibeke
authors.initials: AV
authors.lastname: Laenkholm
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D019715:Tissue Inhibitor of Metalloproteinase-1; C508053:ERBB2 protein, human