title: bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group study.
abstract: OBJECTIVE
  To test the hypothesis that high bcl-2 expression and accumulation of p53 protein, both of which should inhibit apoptosis, are associated with a poorer tamoxifen response and a more aggressive clinical course in estrogen receptor (ER)-positive metastatic breast cancer.
  
  
  METHODS
  A total of 205 paraffin-embedded tumor blocks were evaluated for nuclear p53 (a marker of p53 inactivation) and cytoplasmic bcl-2 by immunohistochemistry (IHC). All patients received tamoxifen as initial therapy for metastatic disease. The study began in 1982 and follow-up duration of the 24 patients last known alive is 8 years.
  
  
  RESULTS
  Response to tamoxifen and time to treatment failure (TTF) were not significantly associated with p53 status, although patients with higher p53 had a worse survival (P = .008; median, 36 v 20 months). Higher bcl-2 expression was associated with higher levels of ER (P = .02), better response to tamoxifen (62% v 49%; P = .07), longer TTF (median, 9 v 5 months; P = .002), and better survival (median, 40 months v 25 months; P = .009). In multivariate analyses, including ER, progesterone receptor (PgR), and p53, high bcl-2 remained significantly associated with a longer TTF (P = .007) and survival (P = .07). p53 status was a significant factor for shorter survival (P = .05), but not for TTF (P = .61).
  
  
  CONCLUSIONS
  p53 status, as determined by IHC is not significantly associated with response to tamoxifen, although tumors with altered p53 protein are inherently more aggressive. Contrary to expectation, high bcl-2 identifies a relatively indolent phenotype of ER-positive metastatic breast cancer, in which patients experience a better clinical response to tamoxifen and a longer survival.
authors.affiliation: University of Texas Health Science Center at San Antonio, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Elledge
authors.forename: S
authors.initials: S
authors.lastname: Green
authors.forename: L
authors.initials: L
authors.lastname: Howes
authors.forename: G M
authors.initials: GM
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Berardo
authors.forename: D C
authors.initials: DC
authors.lastname: Allred
authors.forename: R
authors.initials: R
authors.lastname: Pugh
authors.forename: D
authors.initials: D
authors.lastname: Ciocca
authors.forename: P
authors.initials: P
authors.lastname: Ravdin
authors.forename: J
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: S
authors.initials: S
authors.lastname: Rivkin
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; D013629:Tamoxifen