Coleman R E
Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital NHS Trust, Sheffield, UK.
Eur J Cancer. 2009 Jul;45(11):1909-15. doi: 10.1016/j.ejca.2009.04.022. Epub 2009 May 15.
Great strides have been made over the last 20 years in the treatment of breast cancer and, despite an increasing incidence, the number of deaths has fallen sharply since the late 1980s. The widespread use of new adjuvant therapies including trastuzumab, taxanes and aromatase inhibitors should decrease this even further. However, for women, metastatic breast cancer still remains the number one cause of cancer death in Europe, and the detection and treatment of micrometastatic disease represent the most important challenge in breast cancer management. Bone is the most frequent site of distant relapse, accounting for 30-40% of all first recurrence. In addition to the well-recognised release of bone cell activating factors from the tumour, a wealth of pre-clinical data indicates that the release of bone-derived growth factors and cytokines into the microenvironment can both attract cancer cells to the bone surface and facilitate their growth and proliferation. Bisphosphonates are potent inhibitors of bone osteolysis and may interrupt this so-called 'viscous cycle', thereby impeding both the development of bone metastases and the survival of dormant cells in the marrow microenvironment for the subsequent dissemination to extra-osseus sites. Additionally, the potent amino-bisphosphonates may also have direct effects on tumour cells, especially when administered in combination with chemotherapy. Clinical trial results with the early oral bisphosphonate and clodronate were judged to be inconclusive but the recent data with zoledronic acid suggest that bone targeted treatments may indeed modify the course of the disease. The results of ongoing large metastasis prevention trials are however, required before routine use of adjuvant bisphosphonates can be recommended.
在过去20年里，乳腺癌治疗取得了巨大进展。尽管发病率不断上升，但自20世纪80年代末以来，死亡人数已大幅下降。包括曲妥珠单抗、紫杉烷和芳香化酶抑制剂在内的新辅助治疗方法的广泛应用应会进一步降低死亡率。然而，对于女性而言，转移性乳腺癌仍是欧洲癌症死亡的首要原因，微转移疾病的检测和治疗是乳腺癌管理中最重要的挑战。骨是远处复发最常见的部位，占所有首次复发的30%-40%。除了肿瘤释放骨细胞激活因子这一广为人知的现象外，大量临床前数据表明，骨源性生长因子和细胞因子释放到微环境中，既能吸引癌细胞到骨表面，又能促进其生长和增殖。双膦酸盐是骨溶解的有效抑制剂，可能会中断这种所谓 的“粘性循环”，从而阻碍骨转移的发展以及骨髓微环境中休眠细胞的存活，防止其随后扩散到骨外部位。此外，强效氨基双膦酸盐也可能对肿瘤细胞有直接作用，尤其是与化疗联合使用时。早期口服双膦酸盐氯屈膦酸的临床试验结果尚无定论，但最近唑来膦酸的数据表明，针对骨的治疗可能确实会改变疾病进程。然而，在推荐常规使用辅助性双膦酸盐之前，还需要正在进行的大型转移预防试验的结果。
