Thürlimann B
Department of Internal Medicine, Division of Oncology/Hematology, Kantonsspital, St Gallen, Switzerland.
Ann Oncol. 2007 Sep;18 Suppl 8:viii8-17. doi: 10.1093/annonc/mdm261.
Following primary treatment for early breast cancer, systemic adjuvant therapy is given to reduce the risk of recurrence by targeting any undetectable micrometastatic deposits. Adjuvant systemic treatment may include endocrine therapy, chemotherapy and antibody therapy, depending on the presence or absence of hormone receptors, HER2 status and the estimated risk of relapse. In recent years, an increasing number of tumor characteristics have been identified that influence the risk of relapse and the likelihood of achieving the desired outcome with a given therapy. Hence, choosing the optimum therapy for early breast cancer is becoming an increasingly complicated task. Decision tools have been developed that can be used by physicians to select the most appropriate therapy on an individual basis. Treatment recommendations are, therefore, based on available data from a large number of sources. Hormone-receptor positivity (HR+) is the primary factor when considering whether or not patients should receive adjuvant endocrine therapy. For several decades, tamoxifen has been the gold standard of endocrine therapy, and has significantly reduced recurrences and deaths among the millions of women with HR+ breast cancer worldwide. However, prolonged use of tamoxifen is associated with potentially life-threatening side effects, and resistance is a common problem. In fact, many women will experience disease relapse while on tamoxifen. In particular, the peak of early relapses that occurs in the first 2-3 years after surgery is not prevented by tamoxifen. The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, have recently been shown to significantly improve outcomes compared with tamoxifen in large, randomized, controlled trials; however, how the AIs should be incorporated into adjuvant therapy to optimize outcomes requires further investigation. Clinical differences between the AIs, and whether tumor estrogen/progesterone receptor status and HER2 overexpression affect the response to AI therapy, are among the questions that remain to be answered. Ongoing and future studies will help to address these questions and, together with improved patient and disease profiling, will help physicians to optimize adjuvant treatment for individual patients.
早期乳腺癌经过初始治疗后，会给予全身辅助治疗，通过针对任何无法检测到的微小转移灶来降低复发风险。辅助性全身治疗可能包括内分泌治疗、化疗和抗体治疗，具体取决于激素受体的有无、HER2状态以及估计的复发风险。近年来，已发现越来越多的肿瘤特征会影响复发风险以及采用特定治疗获得理想疗效的可能性。因此，为早期乳腺癌选择最佳治疗方案正变得越来越复杂。已经开发出决策工具，医生可以据此为个体患者选择最合适的治疗方案。所以，治疗建议是基于大量来源的现有数据。在考虑患者是否应接受辅助内分泌治疗时，激素受体阳性（HR+）是主要因素。几十年来，他莫昔芬一直是内分泌治疗的金标准，已显著降低了全球数百万HR+乳腺癌女性的复发率和死亡率。然而，长期使用他莫昔芬会带来潜在的危及生命的副作用，而且耐药是一个常见问题。事实上，许多女性在服用他莫昔芬期间会出现疾病复发。特别是，他莫昔芬无法预防术后头2至3年出现的早期复发高峰。在大型随机对照试验中，与他莫昔芬相比，第三代芳香化酶抑制剂（AIs）来曲唑、阿那曲唑和依西美坦最近已显示出能显著改善治疗效果；然而，如何将AIs纳入辅助治疗以优化疗效仍需进一步研究。AIs之间的临床差异，以及肿瘤雌激素/孕激素受体状态和HER2过表达是否会影响对AI治疗的反应，都是有待解答的问题。正在进行的和未来的研究将有助于解决这些问题，并且与改进的患者和疾病特征分析一起，将帮助医生为个体患者优化辅助治疗。
