title: Prognostic factors for skeletal complications from metastatic bone disease in breast cancer.
abstract: Skeletal morbidity is common in patients with bone metastases from breast cancer (BC) and can undermine patients' functional independence and quality of life. Previously defined prognostic factors may not reflect current treatment standards and the use of antiresorptive therapies. We report a comprehensive multivariate analysis of potential prognostic factors for skeletal-related events (SREs) using data from a phase III, randomized study of zoledronic acid in patients with bone metastases from BC. The trial evaluated the number and timing of SREs (pathologic fracture, palliative radiotherapy to bone, surgery to bone to treat or prevent a fracture, and spinal cord compression) and assessed variables for prognostic significance in univariate and multivariate Cox-regression analyses. Continuous variables were categorized with predefined cutpoints. All associations with P < 0.05 were considered significant. A total of 444 zoledronic acid-treated patients with assessments of biochemical markers of bone metabolism and complete baseline variable data were included. Significant baseline prognostic factors for occurrence of a first SRE by multivariate analyses included age, pain score, prior history of an SRE, predominant lesion type, elevated bone-specific alkaline phosphatase, and lactate dehydrogenase. Prior fracture was found to be prognostic in a reduced multivariate analysis of time to first fracture, but not for time to first palliative radiotherapy. In conclusion, this model identified several prognostic factors that may be useful in routine clinical care. Validation of these factors in a separate dataset and generation of a prognostic risk score are recommended next steps.
authors.affiliation: Cancer Research UK Clinical Centre, University of Leeds, Leeds, UK. 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: Luis
authors.initials: L
authors.lastname: Costa
authors.forename: Robert E
authors.initials: RE
authors.lastname: Coleman
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D017326:Clinical Trials, Phase III as Topic; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D050723:Fractures, Bone / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010146:Pain / Q000209:etiology* / Q000517:prevention & control; D010147:Pain Measurement; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013117:Spinal Cord Compression / Q000209:etiology* / Q000517:prevention & control; D016103:Spinal Fractures / Q000209:etiology / Q000517:prevention & control; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid