Klinikdirektor der Frauenklinik, Klinikum der Heinrich Heine Universität, Moorenstr. 5, 40225 Düsseldorf, Germany.
Cancer Treat Rev. 2010 May;36(3):249-61. doi: 10.1016/j.ctrv.2009.12.010. Epub 2010 Feb 4.
Adjuvant therapy with the third-generation aromatase inhibitors (AIs) anastrozole, letrozole, and exemestane has largely replaced the use of tamoxifen (TAM) as standard adjuvant endocrine treatment for postmenopausal women with hormone-sensitive early breast cancer. Treatment strategies investigated in large, randomized, well-controlled clinical studies include the use of an AI as an upfront replacement for TAM, as an alternative to continued treatment with TAM, and in the extended adjuvant setting after at least 5 years of TAM. The efficacy of AIs over TAM has been demonstrated, particularly in terms of improving disease-free survival (DFS), and reductions in early distant metastasis with AIs may ultimately translate into improved overall survival. As AI therapy offers prolonged DFS, safety is an important concern over the long term. The AIs are better tolerated than TAM in terms of troublesome gynecologic adverse events such as vaginal bleeding and discharge, as well as life-threatening complications such as venous thromboembolic events and endometrial cancer. On the other hand, AI therapy has been associated with losses in bone density and a potential effect on lipids and cardiovascular risk. In trials comparing AIs with TAM, only limited conclusions can be made because of the putative cardioprotective, lipid-lowering, and bone-sparing effects of TAM. Studies comparing AIs with placebo, and/or in healthy women, may be more useful in understanding the long-term safety of adjuvant AI therapy. Results of ongoing safety analyses within some of the large AI trials should provide further insight into the long-term tolerability of AI therapy in the adjuvant setting.
第三代芳香酶抑制剂（AIs）阿那曲唑、来曲唑和依西美坦的辅助治疗已在很大程度上取代了他莫昔芬（TAM）作为激素敏感型早期乳腺癌绝经后妇女的标准辅助内分泌治疗。在大型随机对照临床试验中研究的治疗策略包括将 AI 作为 TAM 的替代物进行一线治疗，作为 TAM 继续治疗的替代物，以及在 TAM 至少 5 年后的延长辅助治疗中使用。AIs 比 TAM 更有效，特别是在改善无病生存期（DFS）方面，并且 AIs 降低早期远处转移的可能性最终可能转化为改善总体生存期。由于 AI 治疗可提供更长的 DFS，因此长期安全性是一个重要问题。在妇科不良事件（如阴道出血和分泌物）和危及生命的并发症（如静脉血栓栓塞事件和子宫内膜癌）方面，AIs 的耐受性优于 TAM。另一方面，AI 治疗与骨密度降低和对脂质和心血管风险的潜在影响有关。在比较 AI 与 TAM 的试验中，由于 TAM 具有潜在的心脏保护、降低血脂和保存骨骼的作用，因此只能得出有限的结论。比较 AI 与安慰剂和/或健康女性的研究可能更有助于了解辅助 AI 治疗的长期安全性。正在进行的一些大型 AI 试验中的安全性分析结果应能更深入地了解辅助 AI 治疗的长期耐受性。
