Department of Gynecology and Obstetrics, University of Duisburg-Essen, D-45122 Essen, Germany.
Oncol Rep. 2013 Jul;30(1):441-7. doi: 10.3892/or.2013.2409. Epub 2013 Apr 22.
Bone is the most common site of metastasis in breast cancer. Detection relies on imaging technology which is costly and can only be performed to a certain degree. Bone markers are non-invasive, inexpensive and may potentially serve as predictive and prognostic surrogate endpoints in detecting bone metastases and response to bisphosphonates. This study analyzed the value of the serum bone turnover markers PINP and ICTP for bone metastases in metastatic breast cancer patients receiving zoledronic acid. The results were compared with the serum levels of CEA and CA 15-3, and analyzed with respect to the number of bone metastases as well as clinical response. Forty patients with confirmed bone metastases who received chemotherapy and/or hormonal therapy and zoledronic acid i.v. q4 weeks participated in the present study. blood (5 ml) was collected at the start of the study and q3 months for a period of one year for the analysis of PINP, ICTP, CEA and CA 15-3 using radioimmunoassays and ELISA, respectively. Imaging of bone metastases was performed at the same time points. In 29 out of 40 patients, more than 3 bone metastases were confirmed by imaging and 11 out of 40 patients presented with 3 or less. At the start of the study, the median value for ICTP was 6 µg/l and for PINP 58.7 µg/l. At the end of the study the median values were 4.5 µg/l for ICTP and 21 µg/l for PINP. When patients were stratified into responders and non-responders, a decrease in both PINP (P<0.0001) and ICTP (P=0.048) was observed for the responders, while the level of ICTP (P=0.02) increased for the non-responders. Serum PINP and ICTP concentrations were significantly different when patients were stratified into groups of those having more than 3 bone metastases and 3 or less, respectively (P<0.05). CEA and CA 15-3 levels did not differ with respect to the number of bone metastases, while the tumor marker levels determined at the end of the study significantly distinguished responders from non-responders (P=0.002 and P=0.004). In conclusion, in contrast to serum tumor markers, the determination of PINP and ICTP allows inferences to the number of bone metastases and appears to be a useful tool for prediction and monitoring metastatic breast cancer patients undergoing bisphosphonate therapy with zoledronic acid for the treatment of bone metastases.
骨是乳腺癌最常见的转移部位。检测依赖于影像学技术，这种技术既昂贵又只能在一定程度上进行。骨标志物是无创的、廉价的，并且可能作为预测和预后的替代终点，用于检测骨转移和对双膦酸盐的反应。本研究分析了血清骨转换标志物 PINP 和 ICTP 在接受唑来膦酸治疗的转移性乳腺癌患者骨转移中的价值。将结果与血清 CEA 和 CA 15-3 的水平进行比较，并根据骨转移的数量以及临床反应进行分析。40 名经组织学或影像学证实的骨转移患者接受化疗和/或激素治疗以及唑来膦酸静脉滴注 q4 周，参与了本研究。在研究开始时和 1 年内的每 3 个月采集 5ml 血液，分别使用放射免疫分析和 ELISA 分析 PINP、ICTP、CEA 和 CA 15-3。同时进行骨转移的影像学检查。在 40 名患者中，有 29 名患者通过影像学检查证实有 3 个以上的骨转移，有 11 名患者有 3 个或更少的骨转移。在研究开始时，ICTP 的中位数为 6µg/L，PINP 的中位数为 58.7µg/L。在研究结束时，ICTP 的中位数为 4.5µg/L，PINP 的中位数为 21µg/L。当患者分为应答者和无应答者时，应答者的 PINP（P<0.0001）和 ICTP（P=0.048）均下降，而无应答者的 ICTP 水平（P=0.02）升高。当患者分为骨转移多于 3 个和 3 个以下的组时，血清 PINP 和 ICTP 浓度差异有统计学意义（P<0.05）。CEA 和 CA 15-3 水平与骨转移的数量无关，而在研究结束时测定的肿瘤标志物水平能显著区分应答者和无应答者（P=0.002 和 P=0.004）。总之，与血清肿瘤标志物相比，PINP 和 ICTP 的测定可以推断出骨转移的数量，并且似乎是预测和监测接受唑来膦酸治疗骨转移的转移性乳腺癌患者的有用工具。
