title: Estrogen receptor and progesterone receptor as predictive biomarkers of response to endocrine therapy: a prospectively powered pathology study in the Tamoxifen and Exemestane Adjuvant Multinational trial.
abstract: OBJECTIVE
  The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included a prospectively planned pathology substudy testing the predictive value of progesterone receptor (PgR) expression for outcome of estrogen receptor-positive (ER-positive) early breast cancer treated with exemestane versus tamoxifen.
  
  
  METHODS
  Pathology blocks from 4,781 TEAM patients randomly assigned to exemestane versus tamoxifen followed by exemestane for 5 years of total therapy were collected centrally, and tissue microarrays were constructed from samples from 4,598 patients. Quantitative analysis of hormone receptors (ER and PgR) was performed by using image analysis and immunohistochemistry, and the results were linked to outcome data from the main TEAM trial and analyzed relative to disease-free survival and treatment.
  
  
  RESULTS
  Of 4,325 eligible ER-positive patients, 23% were PgR-poor (Allred < 4) and 77% were PgR- rich (Allred ≥ 5). No treatment-by-marker effect for PgR was observed for exemestane versus tamoxifen (PgR-rich hazard ratio [HR], 0.83; 95% CI, 0.65 to 1.05; PgR-poor HR, 0.85; 95% CI, 0.61 to 1.19; P = .88 for interaction). Both PgR and ER expression were associated with patient prognosis in univariate (PgR HR, 0.53; 95% CI, 0.43 to 0.65; P < .001; ER HR, 0.66; 95% CI, 0.51 to 0.86; P = .002), and multivariate analyses (P < .001 and P = .001, respectively). A trend toward a treatment-by-marker effect for ER-rich patients was observed.
  
  
  CONCLUSIONS
  Preferential exemestane versus tamoxifen treatment benefit was not predicted by PgR expression; conversely, patients with ER-rich tumors may derive additional benefit from exemestane. Quantitative analysis of ER and PgR expression provides highly significant information on risk of early relapse (within 1 to 3 years) during treatment.
authors.affiliation: Endocrine Cancer Group, Edinburgh Cancer Research Centre, Western General Hospital, Crewe Rd South, Edinburgh, EH4 2XR, United Kingdom. John.Bartlett@ed.ac.uk
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Brookes
authors.forename: Tammy
authors.initials: T
authors.lastname: Robson
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Lucinda J
authors.initials: LJ
authors.lastname: Billingham
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Campbell
authors.forename: Margaret
authors.initials: M
authors.lastname: Grant
authors.forename: Annette
authors.initials: A
authors.lastname: Hasenburg
authors.forename: Elysée T M
authors.initials: ET
authors.lastname: Hille
authors.forename: Charlene
authors.initials: C
authors.lastname: Kay
authors.forename: Dirk G
authors.initials: DG
authors.lastname: Kieback
authors.forename: Hein
authors.initials: H
authors.lastname: Putter
authors.forename: Christos
authors.initials: C
authors.lastname: Markopoulos
authors.forename: Elma Meershoek-Klein
authors.initials: EM
authors.lastname: Kranenbarg
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mallon
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
authors.forename: Caroline
authors.initials: C
authors.lastname: Seynaeve
authors.forename: Daniel
authors.initials: D
authors.lastname: Rea
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018579:Patient Selection; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; C056516:exemestane