乳腺癌骨转移患者溶骨性骨代谢指标与治疗效果的关系

Relationship of osteolytic biochemical indicators of bone metabolism with the therapeutic effect in breast cancer patients with bone metastases

目的探讨特异性的溶骨性骨代谢指标血Ⅰ型胶原吡啶交联羧基末端肽（sICTP）、尿Ⅰ型胶原吡啶交联氨基末端肽（uNTx）和尿吡啶酚（uPyd）与乳腺癌骨转移患者治疗反应的关系。方法应用酶联免疫吸附试验（ELISA），测定120例乳腺癌患者的sICTP、uNTx和uPyd，比较其在骨转移和无骨转移患者中浓度的差别，并对乳腺癌骨转移患者进行随访，比较患者治疗前后sICTP、uNTx和uPyd指标与治疗效果的关系。结果骨转移组患者的sICTP、uNTx和uPyd水平均明显高于无骨转移组（P〈0．01），56例乳腺癌骨转移患者的sICTP、uNTx和uPyd指标间两两相关（均r〉0．5，P〈0．01）。获得随访的45例乳腺癌骨转移患者中，临床受益组25例，sICTP、uNTx和uPyd治疗3个月后明显下降（P=0．025，P〈0．001，P〈0．001）。病情进展组20例，治疗3个月后，sICTP、uNTx和uPyd无明显变化（P〉0．05）；而病情进展后，sICTP、uNTx和uPyd明显升高（P=0．011，P=0．002，P=0．002）。Logistic回归分析结果显示，uPyd和uNTx治疗后降低的患者治疗收益的概率增加（OR=17．0，P=0．019；OR=16．7，P=0．015），而治疗后sICTP指标下降与治疗受益无关（P=0．841）。结论sICTP、uNTx和uPyd可作为乳腺癌骨转移患者评价疗效和转归监测的辅助指标。

Objective The aim of this study was to access the relationship of osteolytic bone metabolic markers such as serum type Ⅰ collagen carboxy-terminal telopeptide （sICTP） , N-terminal cross- linked telopeptides of type Ⅰ collagen （ uNTx）, urinary pyridinoline （uPyd） with the therapeutic effect in breast cancer patients with bone metastases. Methods 120 patients with breast cancer were included in this study. The levels of sICTP, uNTx and uPYD were measured by ELISA assay. The differences were compared between patients with and without bone metastasis. The patients with bone metastasis were treated and followed up as clinically indicated. Results The levels of all above mentioned biomarkers in patients with bone metastasis were significantly higher than that in patients without bone metastasis （ P 〈 0.01 ）. A significant correlation was found between each two markers （r 〉 0.5, P 〈 0. 01 ）. The biomarkers were examined again in 45 patients with bone metastasis after treatment to evaluate the treatment response. The median follow-up was 10 months. Based on clinical evaluation criteria, 25 patients were responders and 20 were non-responders. For responders, after 3 months treatment, the levels of the three bone markers were significantly reduced （P = 0. 025, P 〈 0. 001, P 〈 0. 001 ）. But for non-responders, with progression of bone lesions, the levels of the three markers were significantly raised （P =0.011, P =0.002, P =0.002）. By means of multiple logistic regression with stepwise selection, the uPyd and uNTx activities were closely correlated with treatment response （ OR = 17. 0, P = 0. 019 ; OR = 16.7, P = 0. 015 ） , however, the sICTP did not show any correlation with treatment response P = 0. 841 ）. Conclusion The levels of slCTP, uNTx and uPyd may be used as indicators in assessment of the effect of antiresorptive treatment and evaluation of prognosis in breast cancer patient with bone metastases.