title: Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy.
abstract: BACKGROUND
  Estrogen receptor (ER) status is not an optimal marker for response to adjuvant endocrine therapy since approximately 30% of patients with ER-positive tumors eventually relapse. Bcl-2 is regulated by ER and may thus be considered as an indicator of ER activity and a candidate supplementary marker to ER status.
  
  
  METHODS
  Tumor tissue from 257 patients with ER-positive breast cancer treated with tamoxifen was used for determination of the best threshold for immunohistochemical Bcl-2 assessment as prognostic marker. Subsequently, samples from the Danish patients of the randomized clinical trial BIG 1-98 comprising 1191 ER-positive patients treated with tamoxifen, letrozole or a sequence of the two were immunohistochemically stained for Bcl-2 to further explore the prognostic value of Bcl-2.
  
  
  RESULTS
  Two Bcl-2 levels were found to divide the population of the primary study into significantly different groups according to disease-free survival (DFS). Multivariate analysis confirmed the significance of the lowest level, and showed Bcl-2 to be an independent prognostic marker. Analysis of the Danish cohort of the BIG 1-98 confirmed that Bcl-2 was a significant predictor of DFS, independent of known prognostic markers. However, in an additional analysis of a subset of the Danish cohort of BIG 1-98 including only HER-2 normal patients, the effect of Bcl-2 was not statistically significant.
  
  
  CONCLUSIONS
  Low Bcl-2 can predict poor outcome of patients with ER-positive tumors treated with adjuvant endocrine therapy, whereas the use of Bcl-2 for determination of addition of chemotherapy was not supported by this study.
authors.affiliation: Herlev Hospital, Department of Pathology, Denmark. maskla01@heh.regionh.dk
authors.forename: Mathilde S
authors.initials: MS
authors.lastname: Larsen
authors.forename: Karsten
authors.initials: K
authors.lastname: Bjerre
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Anne-Vibeke
authors.initials: AV
authors.lastname: Lænkholm
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Henriksen
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Anne E
authors.initials: AE
authors.lastname: Lykkesfeldt
authors.forename: Birgitte B
authors.initials: BB
authors.lastname: Rasmussen
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen