title: Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients.
abstract: OBJECTIVE
  Survival is highly variable in women with bone metastases from breast cancer and prognostic factors are needed. We analyzed data from a phase III trial comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer and bone metastases to identify variables prognostic for overall survival.
  
  
  METHODS
  Patients who received ZOL (n = 435) with bone marker assessments and complete baseline data were included. Relative risks (RR) of death over 24 months were assessed using a stratified Cox regression analysis. A reduced model was generated using stepwise backward elimination until only significant (P < 0.05) variables remained.
  
  
  RESULTS
  Only 5 of 19 variables analyzed remained significantly prognostic for survival in the reduced multivariate model. These included age more than 50 years (RR 1.78-2.53, P ≤ 0.01 for each decade >50 versus ≤ 50); Functional Assessment of Cancer Therapy-General (FACT-G) score less than 65 units (P < 0.05 vs. ≥ 75 units); impaired (PS ≥ 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG) performance status (RR 1.74, P < 0.01); prior versus no prior chemotherapy (RR 1.97; P < 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase ≥ upper limit of normal (ULN) but < 2 × ULN correlated with a two-fold increased risk of death, and LDH > 2 × ULN correlated with a six-fold increased risk of death versus LDH < ULN (P < 0.0001 for both). Baseline bone marker levels were not significantly correlated with survival after adjustment for other significant covariates.
  
  
  CONCLUSIONS
  This retrospective analysis shows that LDH levels correlate strongly with survival in patients with bone metastases from breast cancer and confirms the relevance of previously described prognostic factors.
authors.affiliation: Cancer Research UK Experimental Cancer Medicine Centres at Leeds and Sheffield, Cancer Research Centre, Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield, United Kingdom. j.e.brown@leeds.ac.uk
authors.forename: Janet E
authors.initials: JE
authors.lastname: Brown
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cook
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D000077268:Pamidronate; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D007770:L-Lactate Dehydrogenase; D000077268:Pamidronate