乳腺癌内分泌治疗的基本策略分析.pptVIP

谢谢！ 谢谢指导！ 汇报完毕 Estrogen plays several key roles in the induction of breast cancer. These include its mitogenic effects on breast tissue and the mutagenic effects of estrogen’s breakdown products. Together these effects lead to the accumulation of mutations and result in a transformed cancerous morphology with unregulated cell growth and division. Upon its secretion from both reproductive (ovaries) and nonreproductive (muscle, skin fat) tissue, the activity of estrogen (E) is initiated by its binding to its specific receptor (ER), resulting in induction of proliferative and prosurvival signaling cascades, a hallmark of cancer. Given this role of estrogen, 2 approaches have now been adopted to downmodulate estrogen activity Antiestrogens: act as ER antagonists, inhibiting the ER’s ability to bind estrogen and hence abrogating estrogen-mediated signaling (eg, tamoxifen) Aromatase inhibitors: target the aromatase enzyme and prevent the synthesis of estrogen (eg, FEMARA) Tamoxifen was identified as an effective anticancer agent for breast cancer over 25 years ago and has since been used as a standard of care for breast cancer. Aromatase inhibitors such as FEMARA and anastrozole are newer in their clinical development but have now been approved as the first choice for first-line metastatic breast cancer. Aromatase inhibitors have also proved efficacious in adjuvant settings, as will be discussed in the following slides. 乳腺癌内分泌治疗的基本策略 分子靶向 生物治疗 手术 放疗 内分泌治疗 化疗 治 疗 方 法 1896年 Beatson用卵巢切除术治疗乳腺癌肺转移 1939年 Ulrich用雄激素治疗乳腺癌 1940年 Haddow用雌激素治疗乳腺癌 1945年 Huggins用肾上腺切除术治疗转移性乳腺癌 1966年 Jensen发现雌激素受体(ER) 1977年 FDA批准三苯氧胺上市 1992年 高选择性芳香化酶抑制剂兰他隆上市 1981年 氨鲁米特(AG)用于乳腺癌治疗 1984年 甲地孕酮(MA)用于转移性乳腺癌治疗 1998年 第三代高选择性芳香化酶抑制剂上市 内分泌治疗的历史 内分泌治疗生物学机制 绝经的定义 绝经通常是生理性的月经永久性终止，也可以是乳腺癌治疗引起的卵巢合成的雌激素功能永久地丧失。绝经的定义可参考以下几条标准： 双侧卵巢切除术后。 年龄≥60岁。 年龄60岁，且在没有化疗和服用他莫昔芬、托瑞米芬和卵巢功能抑制治疗的情况下停经1年以上，同时血FSH及雌二醇水平符合绝经后的范围；而正在服用他莫昔芬、托瑞米芬，年龄60岁的停经患者，必须连续监测血FSH及雌二醇水平符合绝经后的范围。 绝经的定义 4、正在接受LH-R