title: Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX.
abstract: BACKGROUND
  The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown.
  
  
  METHODS
  We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections.
  
  
  RESULTS
  ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared.
  
  
  CONCLUSIONS
  Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression.
  
  
  BACKGROUND
  Current Controlled Trials ACTRN12607000037404 (Trial VIII) and ACTRN12607000029493 (Trial IX).
authors.forename: Alan S
authors.initials: AS
authors.lastname: Coates
authors.forename: Ewan K A
authors.initials: EK
authors.lastname: Millar
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Molloy
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Richard D
authors.initials: RD
authors.lastname: Gelber
authors.forename: Zhuoxin
authors.initials: Z
authors.lastname: Sun
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione-Gertsch
authors.forename: Barry
authors.initials: B
authors.lastname: Gusterson
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008198:Lymph Nodes; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen; D017273:Goserelin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate