title: Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: results of NCIC CTG MA.14.
abstract: OBJECTIVE
  We investigated the association of bone-only relapse with a pretreatment marker of bone resorption: serum beta C-terminal telopeptide (B-CTx) of type I collagen.
  
  
  METHODS
  Pretreatment serum B-CTx concentrations were determined from 621 of 667 patients with primary breast cancer enrolled onto the NCIC CTG MA.14 phase III adjuvant trial of tamoxifen with or without octreotide. Recurrence-free survival (RFS) was a secondary end point; the focus here was bone-only relapse. We analyzed continuous or categorical (.71 ng/mL cut point) serum B-CTx in stepwise forward multivariate Cox regression, adjusted for trial stratification factors. We also examined B-CTx and bone relapse by pretrial chemotherapy status.
  
  
  RESULTS
  At median 7.9 years follow-up, 123 of 621 patients experienced recurrence; 19 (3.1%) of 621 had bone-only recurrence, and 47 (7.5%) of 621 had bone plus other sites of recurrence. Larger pathologic tumor size (P = .001) and elevated continuous and categorical serum B-CTx were associated with shorter bone-only RFS (both P = .02) when added to a model with factors significant in the main trial analyses (hazard ratio [HR], 3.43 and 3.50, respectively; 95% CI, 1.20 to 9.77 and 1.26 to 9.75, respectively). The univariate HR for B-CTx was 2.80 (95% CI, 1.05 to 7.48; P = .03). Elevated serum B-CTx was also associated with shorter bone-only RFS (P = .02) when added to a model with factors significant in the main trial analyses. Serum B-CTx level was not associated with any other type of recurrence. Serum B-CTx was not significantly different for patients who underwent pretrial chemotherapy, compared with those who did not (P = .27), nor did pretrial chemotherapy affect bone relapse (P = .48 for bone only; P = .76 for bone with other relapse).
  
  
  CONCLUSIONS
  Higher pretreatment serum B-CTx was a significant predictor of shorter RFS for bone-only metastasis. Increased bone resorption creates an environment that promotes growth of breast cancer cells.
authors.affiliation: Penn State Hershey Cancer Institute, Division of Hematology/Oncology, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA. alipton@hmc.psu.edu
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: Judy-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Laurence
authors.initials: L
authors.lastname: Demers
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Wilson
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Kim E
authors.initials: KE
authors.lastname: Leitzel
authors.forename: Suhail M
authors.initials: SM
authors.lastname: Ali
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D001862:Bone Resorption; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D024042:Collagen Type I / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D010455:Peptides / Q000097:blood*; D017698:Postmenopause
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide