Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients

Clin Cancer Res. 2012 Nov 15;18(22):6348-55. doi: 10.1158/1078-0432.CCR-12-1397. Epub 2012 Sep 4.

Abstract

Purpose: 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.

Experimental design: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / blood*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Clinical Trials, Phase III as Topic
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Kaplan-Meier Estimate
  • L-Lactate Dehydrogenase / blood*
  • Middle Aged
  • Multivariate Analysis
  • Pamidronate
  • Prognosis
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Treatment Outcome
  • Zoledronic Acid

Substances

  • Antineoplastic Agents
  • Diphosphonates
  • Imidazoles
  • Zoledronic Acid
  • L-Lactate Dehydrogenase
  • Pamidronate