title: Effect of tibolone on breast cancer cell proliferation in postmenopausal ER+ patients: results from STEM trial.
abstract: OBJECTIVE
  Tibolone is a selective tissue estrogenic activity regulator, approved for the treatment of vasomotor symptoms in postmenopausal women. We have done an exploratory, double-blind, randomized, placebo-controlled pilot trial to investigate the tissue-specific effects of 2.5 mg tibolone on breast cancer in postmenopausal women, in particular on tissue proliferation (STEM, Study of Tibolone Effects on Mamma carcinoma tissue).
  
  
  METHODS
  Postmenopausal women with initially stage I/II, estrogen receptor-positive (ER+) primary breast cancer, were randomly assigned to 14 days of placebo or 2.5 mg/d tibolone. Core biopsies of the primary tumor were obtained before and after treatment. Ki-67 and apoptosis index were analyzed in baseline and corresponding posttreatment specimen.
  
  
  RESULTS
  Of 102 enrolled patients, 95 had evaluable data. Baseline characteristics were comparable between both treatment groups. Breast cancer cases are mainly invasive (99%), stage I or II (42% and 50% respectively), and ER+ (99%). Median intratumoral Ki-67 expression at baseline was 13.0% in the tibolone group and 17.8% in the placebo group, and decreased to 12.0% after 14 days of tibolone while increasing to 19.0% in the placebo group. This change from baseline was not significantly different between tibolone and placebo (Wilcoxon test; P=0.17). A significant difference was observed between the treatment groups when the median change from baseline apoptosis index was compared between the treatment groups (tibolone, 0.0%; placebo, +0.3%; Wilcoxon test; P=0.031). The incidence of adverse effects was comparable.
  
  
  CONCLUSIONS
  In ER+ breast tumors, 2.5 mg/d tibolone given for 14 days has no significant effect on tumor cell proliferation.
authors.affiliation: Division of Special Gynecology, Medical University of Vienna, Vienna, Austria.
authors.forename: Ernst
authors.initials: E
authors.lastname: Kubista
authors.forename: Juan V M
authors.initials: JV
authors.lastname: Planellas Gomez
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Kamil
authors.initials: K
authors.lastname: Pohlodek
authors.forename: Rudolphe
authors.initials: R
authors.lastname: Serreyn
authors.forename: Michail
authors.initials: M
authors.lastname: Nechushkin
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Manikhas
authors.forename: Victor F
authors.initials: VF
authors.lastname: Semiglazov
authors.forename: Cornelius C M
authors.initials: CC
authors.lastname: Hageluken
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
mesh_terms: D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D017698:Postmenopause; D012449:Safety
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009652:Norpregnenes; D010919:Placebos; C027385:tibolone