Buzdar Aman U, Coombes R Charles, Goss Paul E, Winer Eric P
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Department of Medical Oncology, Imperial College School of Medicine, London, United Kingdom.
Cancer. 2008 Feb 1;112(3 Suppl):700-709. doi: 10.1002/cncr.23193.
Five years of adjuvant therapy with tamoxifen was considered the gold-standard treatment for postmenopausal women with estrogen receptor-positive breast cancer for many years. Data from a core group of clinical trials investigating the safety and efficacy of aromatase inhibitors (AIs) have challenged this perception. These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98), 2) in a "switched setting" after 2 to 3 years of treatment with tamoxifen (Arimidex-Nolvadex 95, the Austrian Breast and Colorectal Cancer Study Group 8 [ABCSG 8] trial, the Italian Tamoxifen Anastrozole study, the Intergroup Exemestane Study), and 3) in extended settings (National Cancer Institute of Canada Trial MA.17, ABCSG 6a, National Surgical Adjuvant Breast and Bowel Project 33). The efficacy data from these studies suggested that AIs have added substantial benefit in terms of disease outcome. AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen. However, patients who received tamoxifen had less skeletal events and accelerated bone resorption compared with women who received AIs. AIs should be considered when planning a patient's endocrine therapy, taking into account the differences in tolerability and end-organ effects of the classes of endocrine therapy. Outstanding issues to optimize AI therapy include identifying the optimal duration, agent, and patients for these therapies.
多年来，他莫昔芬辅助治疗5年一直被视为绝经后雌激素受体阳性乳腺癌女性的金标准治疗方法。一组核心临床试验关于芳香化酶抑制剂（AIs）安全性和疗效的数据对这一观念提出了挑战。这些研究旨在评估AIs在以下临床情况下的安全性和疗效：1）作为初始辅助治疗（阿那曲唑、他莫昔芬单药或联合治疗试验，国际乳腺癌研究组试验1-98）；2）在接受他莫昔芬治疗2至3年后的“转换治疗”中（阿那曲唑-他莫昔芬95，奥地利乳腺癌和结直肠癌研究组8[ABCSG 8]试验，意大利他莫昔芬阿那曲唑研究，国际 exemestane 研究组试验）；3）在延长治疗中（加拿大国家癌症研究所试验MA.17，ABCSG 6a，国家外科辅助乳腺和肠道项目33）。这些研究的疗效数据表明，AIs在疾病转归方面带来了显著益处。AIs耐受性良好，与接受他莫昔芬治疗的患者相比，接受AIs治疗的患者发生血栓事件较少，子宫内膜癌、潮热、盗汗和阴道出血也较少。然而，与接受AIs治疗的女性相比，接受他莫昔芬治疗的患者骨骼事件较少，骨吸收加速。在规划患者的内分泌治疗时，应考虑到内分泌治疗类别在耐受性和靶器官效应方面的差异，考虑使用AIs。优化AI治疗的突出问题包括确定这些治疗的最佳持续时间、药物和患者。
