双膦酸盐辅助治疗在早期乳腺癌患者中的应用推荐.pptVIP

* * * Metastasis to bone occurs via a multi-step process, and inhibition of any of these steps could prevent metastasis to bone1 The primary malignant neoplasm promotes new blood vessel formation (angiogenesis) Cancer cells must then invade the blood vessels, wherein they form multi-celled aggregates Aggregates of tumor cells form emboli that lodge in capillary beds in bone Cancer cells can adhere to vascular epithelial cells to escape the blood vessels and must extravasate through the extracellular matrices to enter the bone microenvironment As cancer cells enter the bone, they are exposed to factors in the bone microenvironment, such as growth factors released from the bone matrix during osteolysis, which may promote tumor growth Zoledronic acid can inhibit multiple steps in the metastatic process and has demonstrated direct and indirect antitumor activities in preclinical assays2 Reference Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584-593. Lipton A. Emerging role of bisphosphonates in the clinic-Antitumor activity and prevention of metastasis to bone. Cancer Treat Rev. 2008. May 15. [Epub ahead of print] * The study endpoints defined for endocrine therapy alone and in combination with zoledronic acid. The endpoints consist of disease-free, recurrence-free, and overall survivals in addition to exploratory endpoints. * * * * * * * Zoledronic acid improved disease-free survival by a relative 36% (P = .012) compared with placebo over 84 months with a median follow-up of 60 months Patients treated with zoledronic acid experienced only 54 events compared with 83 events experienced in patients with no zoledronic acid These results may reflect the antitumor activity of zoledronic acid and its potential to alter the disease course for patients with early cancer Reference Gnant M, Mlineritsch B, Schippinger W, et al. Adjuvant ovarian suppression combined with tamoxifen or anastrozole, alone or in combin