title: Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness-a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer.
abstract: BACKGROUND
  The role of estrogen receptor beta (ER-β) in breast cancer (BC) remains unclear. Some studies have suggested that ER-β may oppose the actions of estrogen receptor alpha (ER-α), and clinical evidence has indicated that the loss of ER-β expression is associated with a poor prognosis and resistance to endocrine therapy. The objective of the present study was to determine the role of ER-β and the ER-α/ER-β ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-β expression levels.
  
  
  METHODS
  Ninety postmenopausal patients with primary BC were recruited for a short-term double-blinded randomized prospective controlled study. To determine tumor cell proliferation, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of treatment with anastrozole 1 mg/day (N = 25), tamoxifen 20 mg/day (N = 24) or placebo (N = 29) of 78 participants. The pre- and post-samples were placed in tissue microarray blocks and submitted for immunohistochemical assay. Biomarker statuses (ER-β, ER-α and Ki67) were obtained by comparing each immunohistochemical evaluation of the pre- and post-surgery samples using the semi-quantitative Allred's method. Statistical analyses were performed using an ANOVA and Spearman's correlation coefficient tests, with significance at p ≤ 0.05.
  
  
  RESULTS
  The frequency of ER-β expression did not change after treatment (p = 0.33). There were no significant changes in Ki67 levels in ER-β-negative cases (p = 0.45), but in the ER-β-positive cases, the anastrozole (p = 0.01) and tamoxifen groups (p = 0.04) presented a significant reduction in post-treatment Ki67 scores. There was a weak but positive correlation between the ER-α and ER-β expression levels. Only patients with an ER-α/ER-β expression ratio between 1 and 1.5 demonstrated significant differences in Ki67 levels after treatment with anastrozole (p = 0.005) and tamoxifen (p = 0.026).
  
  
  CONCLUSIONS
  Our results provide additional data that indicate that the measurement of ER-β in BC patients may help predict tamoxifen and anastrozole responsiveness in the neoadjuvant setting. These effects of hormonal treatment appear to be dependent on the ratio of ER-α/ER-β expression.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN89801719.
authors.affiliation: Senology Discipline, Department of Gynecology, Federal University of Sao Paulo-UNIFESP, R, Botucatu, 740, 04023-900 Sao Paulo, SP, Brazil. marcemadeira@gmail.com.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Madeira
authors.forename: André
authors.initials: A
authors.lastname: Mattar
authors.forename: Angela Flávia
authors.initials: AF
authors.lastname: Logullo
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Luiz Henrique
authors.initials: LH
authors.lastname: Gebrim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage* / Q000627:therapeutic use; D017698:Postmenopause; D011379:Prognosis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole
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