title: Time-dependent relevance of steroid receptors in breast cancer.
abstract: OBJECTIVE
  To analyze the time-dependent prognostic role of the investigated variables, considered, when appropriate, on a continuous scale, for the purpose of evaluating and describing the interrelationships between clinically relevant patient and tumor characteristics (age, size and histology, and estrogen receptor [ER] and progesterone receptor content) and the risk of new disease manifestation.
  
  
  METHODS
  We applied a flexible statistical model to a case series of 1,793 patients with axillary lymph node-negative breast cancer with a minimal potential follow-up of 10 years. To avoid a potential confounding effect of adjuvant treatment, only patients given local-regional therapy until relapse were considered.
  
  
  RESULTS
  ER content and tumor size (adjusted for all the other covariates) showed a time-dependent relationship with the risk of new disease manifestations. In particular, ER content failed to show a prognostic effect within the first years of follow-up; thereafter, a positive association with risk of relapse was observed. For tumor size, within the first years of follow-up, the risk of relapse was directly related to size for only tumors up to 2.5 cm in diameter; thereafter, the impact on prognosis progressively decreased.
  
  
  CONCLUSIONS
  The availability of a long follow-up on a large breast cancer series, as well as the use of innovative statistical approaches, allowed us to explore the functional relation between steroid receptors and clinical outcome and to generate a hypothesis on the involvement of ER in favoring long-term metastasis development.
authors.affiliation: Unità Operativa Determinanti Biomolecolari nella Prognosi e Terapia, Milan, Italy. coradini@istitutotumori.mi.it
authors.forename: D
authors.initials: D
authors.lastname: Coradini
authors.forename: M G
authors.initials: MG
authors.lastname: Daidone
authors.forename: P
authors.initials: P
authors.lastname: Boracchi
authors.forename: E
authors.initials: E
authors.lastname: Biganzoli
authors.forename: S
authors.initials: S
authors.lastname: Oriana
authors.forename: G
authors.initials: G
authors.lastname: Bresciani
authors.forename: C
authors.initials: C
authors.lastname: Pellizzaro
authors.forename: G
authors.initials: G
authors.lastname: Tomasic
authors.forename: G
authors.initials: G
authors.lastname: Di Fronzo
authors.forename: E
authors.initials: E
authors.lastname: Marubini
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011987:Receptors, Steroid; D013997:Time Factors
chemical_list: D011987:Receptors, Steroid