张丽娜, 杨艳芳, 顾林. 唑来膦酸在早期乳腺癌中的抗肿瘤研究进展[J]. 中国肿瘤临床, 2013, 40(16): 1005-1007. DOI: 10.3969/j.issn.1000-8179.20130676
引用本文: 张丽娜, 杨艳芳, 顾林. 唑来膦酸在早期乳腺癌中的抗肿瘤研究进展[J]. 中国肿瘤临床, 2013, 40(16): 1005-1007. DOI: 10.3969/j.issn.1000-8179.20130676
Lina ZHANG, Yanfang YANG, Lin GU. Research progress in antitumor effects of zoledronic acid in early breast cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2013, 40(16): 1005-1007. DOI: 10.3969/j.issn.1000-8179.20130676
Citation: Lina ZHANG, Yanfang YANG, Lin GU. Research progress in antitumor effects of zoledronic acid in early breast cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2013, 40(16): 1005-1007. DOI: 10.3969/j.issn.1000-8179.20130676

唑来膦酸在早期乳腺癌中的抗肿瘤研究进展

Research progress in antitumor effects of zoledronic acid in early breast cancer

  • 摘要: 早期乳腺癌在接受辅助治疗(化疗和内分泌治疗)时均会对患者骨密度造成不良影响,加速骨丢失。第三代双磷酸盐—唑来膦酸其作用机制是抑制破骨细胞介导的骨质重吸收,主要用于恶性肿瘤骨转移引起的高钙血症。唑来膦酸-弗隆辅助协同试验(ZO-FAST)显示唑来膦酸在早期乳腺癌辅助内分泌治疗同时使用不仅可有效防止骨质丢失,还具有明显降低肿瘤复发的作用。奥地利乳腺癌和结直肠癌研究小组-12(ABCSG-12)试验结果同样表明唑来膦酸在联合内分泌治疗时可显著降低患者的疾病进展风险和死亡风险。除此之外,临床前实验和临床试验也证实唑来膦酸联合化疗也具有协同的抗肿瘤作用。唑来膦酸联合新辅助化疗降低复发(AZURE试验),对于绝经5年以上和年龄>60岁的人群,辅助化疗加唑来膦酸显著减低疾病进展和死亡风险。在ABCSG-12试验中同样发现对于年龄>40岁的患者,唑来膦酸可明显降低复发风险,而年龄≤40岁患者却未在唑来膦酸的治疗中获益。这些结果表明唑来膦酸在雌激素低水平(自然的或治疗后结果)的早期乳腺癌患者中易于发挥抗肿瘤作用。目前对于唑来膦酸的最佳剂量和持续时间尚有待于进一步的研究确认,相信随着相关临床试验结果的公布可以提供更充足的证据来支持唑来膦酸在早期乳腺癌的使用。

     

    Abstract: Adjuvant treatment, which includes chemotherapy and endocrine therapy, for early breast cancer may impair bone density, resulting in bone loss. The third generation bisphosphonate-zoledronic is an anti-resorptive agent that inhibits osteoclast-mediated bone resorption. This drug can be mainly used in the treatment of hypercalcemia caused by bone metastases of the cancer. The Zometa- Femara Adjuvant Synergy Trial revealed that immediate zoledronic acid and endocrine therapy not only prevents bone loss, but also reduces recurrence. The Austrian Breast and Colorectal Cancer Study Group-12 (ABCSG-12) also confirmed that zoledronic acid, when combined with endocrine therapy, could reduce the risk of cancer disease progression and death. Moreover, preclinical studies and clinical trials have demonstrated the synergistic antitumor effects of chemotherapy and zoledronic acid. Neo-adjuvant zoledronic acid to reduce recurrence trials showed that the addition of zoledronic acid to adjuvant chemotherapy significantly reduced the risk of disease progression and death in postmenopausal women more than five years postmenopause at the beginning of the study or over 60 years of age at the baseline. The ABCSG-12 subgroup analysis based on age (≤40 years or >40 years) also showed that zoledronic acid can significantly improve the prognosis in women who were over 40 years at the study entry. These results suggest that zoledronic acid administration in patients with lowered estrogen levels (naturally or as a consequence of adjuvant treatment) easily exerts anti-tumor effects. However, the optimal dose and duration of zoledronic acid requires further studies. More clinical trials should be performed to provide sufficient evidence to support the effectiveness of zoledronic acid in the treatment of early breast cancer.

     

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