Serum Lactate Dehydrogenase Is Prognostic for Survival in Patients with Bone Metastases from Breast Cancer: A Retrospective Analysis in Bisphosphonate-Treated Patients

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: PatientswhoreceivedZOL(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 x ULN correlated with a two-fold increased risk of death, and LDH > 2 x 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. Clin Cancer Res; 18(22); 6348-55. (C) 2012 AACR.