Nishimukai Arisa, Higuchi Tomoko, Ozawa Hiromi, Yanai Ayako, Miyagawa Yoshimasa, Murase Keiko, Imamura Michiko, Takatsuka Yuichi, Miyoshi Yasuo
Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
Breast Cancer. 2017 Mar;24(2):245-253. doi: 10.1007/s12282-016-0695-2. Epub 2016 Apr 4.
Bone-modifying agents are effective for treatment of breast cancer patients with bone metastases. Since their action is mediated through suppression of the osteoclast function, their efficacy can be determined by monitoring bone turnover markers. However, the clinical significance of these markers is yet to be compared.
For this study, 52 breast cancer patients with bone metastases treated with zoledronic acid (n = 36) or denosumab (n = 22) were enrolled (6 patients were treated sequentially with both agents). Serum tartrate-resistant acid phosphatase-5b (TRACP-5b), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), N-terminal cross-linking telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) were measured at pretreatment and 1, 3 and 6 months after treatment.
Serum TRACP-5b (p < 0.0001), NTX (p = 0.0007) and BAP (p = 0.0032) decreased significantly after treatment. The baseline median value of TRACP-5b (457.5 mU/dL, range 173-1630 mU/dL) decreased to 137 mU/dL (91-795 mU/dL) 1 month after treatment. Reduction in serum NTX and BAP was greatest after 3 and 6 months, respectively. TRACP-5b, NTX and BAP were above normal levels at baseline in 62.5, 25 and 35.3 % of patients, respectively, and nearly 80 % of these patients attained normal levels during the treatment.
Although bone-modifying agents reduced the baseline levels of TRACP-5b, NTX and BAP significantly, the reduction patterns differed. TRACP-5b appears to affect levels most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings suggest that the efficacy of TRACP-5b is clinically significant when considering which bone-modifying agents to use for breast cancer patients with bone metastases.
骨修饰剂对治疗有骨转移的乳腺癌患者有效。由于其作用是通过抑制破骨细胞功能介导的，其疗效可通过监测骨转换标志物来确定。然而，这些标志物的临床意义尚待比较。
本研究纳入了52例接受唑来膦酸（n = 36）或地诺单抗（n = 22）治疗的有骨转移的乳腺癌患者（6例患者先后接受了两种药物治疗）。在治疗前以及治疗后1、3和6个月测量血清抗酒石酸酸性磷酸酶-5b（TRACP-5b）、I型胶原吡啶交联羧基末端肽（1CTP）、I型胶原N末端交联肽（NTX）和骨特异性碱性磷酸酶（BAP）。
治疗后血清TRACP-5b（p < 0.0001）、NTX（p = 0.0007）和BAP（p = 0.0032）显著降低。治疗1个月后，TRACP-5b的基线中位数（457.5 mU/dL，范围173 - 1630 mU/dL）降至137 mU/dL（91 - 795 mU/dL）。血清NTX和BAP分别在3个月和6个月后降低最为明显。分别有62.5%、25%和35.3%的患者基线时TRACP-5b、NTX和BAP高于正常水平，且这些患者中近80%在治疗期间达到正常水平。
虽然骨修饰剂显著降低了TRACP-5b、NTX和BAP的基线水平，但降低模式有所不同。TRACP-5b似乎对水平的影响最快且最敏感，这可能是由于它与破骨细胞的数量和活性直接相关。这些发现表明，在考虑为有骨转移的乳腺癌患者使用哪种骨修饰剂时，TRACP-5b的疗效具有临床意义。
