Penn State Hershey Cancer Institute, Division of Hematology/Oncology, Penn State Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA.
J Clin Oncol. 2011 Sep 20;29(27):3605-10. doi: 10.1200/JCO.2010.31.5069. Epub 2011 Aug 22.
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.
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.
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).
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.
我们研究了与骨复发相关的一种骨吸收预处理标志物：I 型胶原β C 末端肽（B-CTX）。
从纳入 NCIC CTG MA.14 期三苯氧胺辅助试验的 667 例原发性乳腺癌患者中的 621 例患者中测定了预处理血清 B-CTX 浓度。无病生存（DFS）是次要终点；这里的重点是骨复发。我们使用逐步向前多变量 Cox 回归分析了连续或分类（71ng/ml 切点）血清 B-CTX，调整了试验分层因素。我们还检查了术前化疗状态下的 B-CTX 和骨复发。
中位随访 7.9 年后，621 例患者中有 123 例复发；621 例中有 19 例（3.1%）发生骨复发，621 例中有 47 例（7.5%）发生骨加其他部位复发。更大的病理肿瘤大小（P=0.001）和升高的连续和分类血清 B-CTX 与较短的骨复发 DFS 相关（均 P=0.02），当添加到主试验分析中有意义的因素模型中（风险比[HR]分别为 3.43 和 3.50；95%CI，分别为 1.20 至 9.77 和 1.26 至 9.75）。B-CTX 的单变量 HR 为 2.80（95%CI，1.05 至 7.48；P=0.03）。升高的血清 B-CTX 与较短的骨复发 DFS 相关（P=0.02），当添加到主试验分析中有意义的因素模型中时。血清 B-CTX 水平与任何其他类型的复发无关。与未接受术前化疗的患者相比，接受术前化疗的患者的血清 B-CTX 水平无显著差异（P=0.27），术前化疗也不影响骨复发（骨复发时 P=0.48；骨复发加其他部位复发时 P=0.76）。
较高的预处理血清 B-CTX 是骨转移无病生存较短的显著预测因子。骨吸收增加会产生促进乳腺癌细胞生长的环境。
