Elevated bone turnover predicts for bone metastasis in postmenopausal breast cancer: Results of NCIC CTG MA.14

Purpose: 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). Conclusion: 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.