乳腺癌辅助内分泌治疗2014.ppt

* * Goss et al. N Engl J Med. 2003;349:1793.Goss et al. J Natl Cancer Inst. 2005;97:1262. * * * * Ingle et al. Ann Oncol. 2008;19:877. * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Exemestane 25 mg/day (n = 799) Placebo(n = 799) Postmenopausal women with T1-3 N0-1 M0 breast cancer, disease free after 5 years of tamoxifen (N = 1598; target accrual, N = 3000) Year 5 *NCIC MA.17 trial results released in October 2003, showing benefit for aromatase inhibitor made it unethical to continue patients on placebo alone. After unblinding, 560 of 783 patients receiving exemestane continued on exemestane and 344 of 779 patients initially receiving placebo switched to exemestane. Study unblinded and accrual stopped in October 2003* Median follow-up: 30 months Mamounas E, et al. SABCS 2006. Abstract 48. NSABP B-33: Exemestane Treatment Following 5 Years of Tamoxifen NSABP B-33:无事件生存 Mamounas EP, et al. J Clin Oncol. 2008;26(12):1965-71. 无复发生存 无病生存 Group n Events Placebo 779 13 Exemestane 783 16 98% 95% RR: 120 P = .63 Patients* (%) Years After Randomization 0 1 2 3 4 5 0 20 40 60 80 100 NSABP B-33: Small Effects of Exemestane on Overall Survival * Eligible pts with follow-up Mamounas EP, et al. J Clin Oncol. 2008;26(12):1965-71. 早期乳腺癌术后辅助内分泌治疗总结 内分泌治疗的策略 1.调节雌激素受体： 选择性雌激素受体抑制剂 （SERMs）:三苯氧胺﹑托瑞米芬 (法乐通﹑枢瑞) 选择性雌激素受体下调剂 （SERDs）:faslodex 2.阻断雌激素合成 双侧卵巢切除术（绝经前） 芳香化酶抑制剂（AI）（绝经后）:一代 氨鲁米特 二代 fadrozole(法倔唑) 三代 瑞宁得(阿那曲唑)﹑弗隆(来曲唑) 芳香化酶灭活剂:一代 睾内酯 二代 福美司坦(兰他隆) 三代 阿诺新(依西美坦) 其它激素治疗（如甲地孕酮 、雄激素和雌激素） 3.抑制下丘脑－垂体－卵巢的功能，药物性去势－降低循环血内雌激素水平等:促黄体生成激素释放激素类似物【戈舍瑞林(诺雷得)、曲普瑞林】 促黄体生成激素释放激素类似物作用原理 LHRH (下丘脑) 脑垂体内分泌腺 雌激素 孕激素 卵巢 下调LH-RH受体 促性腺激素 (FSH + LH) Pagani O,et al. N Engl J Med. 2014 ;371