Perez E A
Mayo Clinic, Jacksonville, FL, USA.
Ann Oncol. 2007 Sep;18 Suppl 8:viii26-35. doi: 10.1093/annonc/mdm263.
Adjuvant endocrine therapy plays an important role in the management of hormone-receptor-positive early breast cancer, and has increased life expectancy for millions of women. Many patients receive adjuvant treatment for at least 5 years following tumor resection, hence good long-term safety is important for endocrine agents to gain widespread acceptance. Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile limits treatment duration to 5 years. Increased efficacy over tamoxifen and good tolerability have recently made the third-generation aromatase inhibitors (AIs) the first-choice agents for adjuvant endocrine therapy; however, it is currently not known whether AI therapy, like tamoxifen, will be limited to 5 years. Many side effects of endocrine therapy, such as hot flushes and mood disturbances, are related to estrogen deprivation and are common to tamoxifen and AIs, reflecting the mechanism of action of these drugs. In addition, tamoxifen has estrogenic effects that are beneficial in some tissues: tamoxifen lowers serum cholesterol levels and protects against bone loss and cardiovascular disease, but is also associated with potentially life-threatening side effects, such as endometrial cancer and thromboembolic disease. As AIs lack estrogenic activity, they are not associated with these serious adverse events. Clinical trials comparing AIs with tamoxifen in the adjuvant setting have shown that AIs are well tolerated and are associated with a lower incidence of gynecological symptoms and hot flushes than tamoxifen. However, AIs are associated with musculoskeletal side effects, such as arthralgia, myalgia and bone loss, but these events are preventable or manageable. The effects of AIs on lipid metabolism and the cardiovascular system are still debatable, but placebo-controlled trials provide no evidence to suggest that AIs adversely affect these systems. Furthermore, the AIs allow women to maintain a good quality of life, comparable with women receiving tamoxifen or placebo, and are a cost-effective therapeutic option. Ongoing trials will provide more information regarding the long-term effects of AI therapy and will provide comparative data on the efficacy and safety of the different AIs, thereby helping to determine the optimal treatment strategy for these highly effective and well-tolerated drugs.
辅助内分泌治疗在激素受体阳性早期乳腺癌的治疗中发挥着重要作用，使数百万女性的预期寿命得以延长。许多患者在肿瘤切除后接受至少5年的辅助治疗，因此内分泌药物良好的长期安全性对于其获得广泛应用至关重要。他莫昔芬作为早期乳腺癌的辅助治疗药物已使用多年，安全性数据记录完善，但风险效益比不佳限制了治疗疗程至5年。与他莫昔芬相比疗效提高且耐受性良好，使得第三代芳香化酶抑制剂（AIs）成为辅助内分泌治疗的首选药物；然而，目前尚不清楚AI治疗是否会像他莫昔芬一样限于5年疗程。内分泌治疗的许多副作用，如潮热和情绪紊乱，与雌激素缺乏有关，是他莫昔芬和AIs共有的，反映了这些药物的作用机制。此外，他莫昔芬具有在某些组织中有益的雌激素样作用：他莫昔芬可降低血清胆固醇水平，预防骨质流失和心血管疾病，但也与潜在的危及生命的副作用相关，如子宫内膜癌和血栓栓塞性疾病。由于AIs缺乏雌激素活性，它们与这些严重不良事件无关。在辅助治疗中比较AIs与他莫昔芬的临床试验表明，AIs耐受性良好，与他莫昔芬相比，妇科症状和潮热的发生率更低。然而，AIs与肌肉骨骼副作用相关，如关节痛、肌痛和骨质流失，但这些事件是可预防或可控制的。AIs对脂质代谢和心血管系统的影响仍存在争议，但安慰剂对照试验没有证据表明AIs会对这些系统产生不利影响。此外，AIs能使女性维持良好的生活质量，与接受他莫昔芬或安慰剂的女性相当，是一种具有成本效益的治疗选择。正在进行的试验将提供更多关于AI治疗长期效果的信息，并将提供不同AIs疗效和安全性的比较数据，从而有助于确定这些高效且耐受性良好药物的最佳治疗策略。
