将近四分之三的乳腺癌为激素受体阳性且HER2阴性，其主要治疗方法为内分泌治疗。虽然内分泌治疗，例如氟维司群，被广泛用于临床，但是内分泌耐药（原发性或继发性）难以避免并且成为严重的临床问题。不过，激素受体阳性HER2阴性乳腺癌的治疗方案正在迅速变化和革新。近年来，对于激素受体阳性HER2阴性乳腺癌基因组的分子学探索，有助于确定有希望的靶点，例如信号通路改变（PI3K → AKT → mTOR）、细胞有丝分裂周期蛋白依赖型激酶（CDK4/6）失调、雌激素受体编码基因1（ESR1）突变。这些探索促进了新型靶向治疗药物的开发，可以显著改善这些患者的生存，例如氟维司群。
2019年4月19日，美国癌症学会和国际抗癌联盟《癌症医学》在线发表复旦大学附属肿瘤医院李俊杰、王中华、邵志敏等学者的综述，总结了氟维司群单药或联合靶向治疗对于激素受体阳性HER2阴性晚期乳腺癌患者的作用和机制，还讨论了其他新药和潜在的未来联合治疗方案。
氟维司群作用示意图
AF1：雌激素受体转录激活功能区1；AF2：雌激素受体转录激活功能区2；ER：雌激素受体；ERE：雌激素受体反应元件；F：氟维司群；RNA POL II：核糖核酸聚合酶II
氟维司群II/III期随机对照研究
CDK：细胞有丝分裂周期蛋白依赖型激酶；CBR：临床获益率；ORR：总缓解率；EGFR：表皮生长因子受体；F：氟维司群；HER2：人类表皮生长因子受体2型；IGFR：胰岛素样生长因子受体；mTOR：哺乳动物雷帕霉素靶蛋白；N：患者数量；OS：总生存；PFS：无进展生存；PI3K：磷脂酰肌醇3-激酶
氟维司群以及其他靶向治疗对癌细胞的作用机制
AKT：蛋白激酶B；CDK4/6：细胞有丝分裂周期蛋白依赖型激酶4/6；EGFR：表皮生长因子受体；HER2/3：人类表皮生长因子受体2/3型；IGFR：胰岛素样生长因子受体；mTOR：哺乳动物雷帕霉素靶蛋白；PI3K：磷脂酰肌醇3-激酶；OR：雌激素受体
CDK4/6抑制剂＋氟维司群II/III/IV期关键临床研究
AI：芳香酶抑制剂；BC：乳腺癌；CDK：细胞有丝分裂周期蛋白依赖型激酶；CBR：临床获益率；HER2：人类表皮生长因子受体2型；HR：激素受体；HRQOL：健康相关生活质量；OS：总生存；ORR：总缓解率；PFS：无进展生存；QOL：生活质量；TTF：治疗失败时间；TTP：进展时间
PI3Kα抑制剂＋氟维司群III期临床研究
AI：芳香酶抑制剂；CBR：临床获益率；HER2：人类表皮生长因子受体2型；HR：激素受体；OS：总生存；ORR：总缓解率；PFS：无进展生存；QOL：生活质量
mTOR抑制剂＋氟维司群II期临床研究
AE：不良事件；BC：乳腺癌；CBR：临床获益率；HER2：人类表皮生长因子受体2型；HR：激素受体；ORR：总缓解率；PFS：无进展生存
Cancer Med. 2019 Apr 19. [Epub ahead of print]
Fulvestrant in the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: A review.
Li J, Wang Z, Shao Z.
Fudan University Shanghai Cancer Center, Shanghai, China.
Nearly 75% of breast cancers are hormone receptor-positive (HR+) and human epidermal growth factor receptor type 2-negative (HER2-), making endocrine therapy the mainstay of treatment for HR+ and HER2- combination. Although endocrine therapy, such as therapy with fulvestrant, is widely used in the clinic, endocrine resistance (primary or secondary) is inevitable and poses a serious clinical concern. However, the therapeutic landscape of HR+/HER2- breast cancer is rapidly changing and evolving. In recent years, molecular insights into the genome of HR+/HER2- breast cancer have helped to identify promising targets, such as alterations in signaling pathways [phosphatidylinositide 3-kinase (PI3K/AKT/mammalian target of rapamycin (mTOR)], dysregulation of the cell cycle (CDK4/6), and identification of new ESR1 mutations. These insights have led to the development of newer targeted therapies, which aims at significantly improving survival in these patients. This review summarizes the role and rationale of fulvestrant when used as a monotherapy or in combination with targeted therapies in patients with HR+/HER2- advanced breast cancer. We also discuss other novel agents and potential future combination treatment options.
KEYWORDS: HER2-; HR+; advanced breast cancer; fulvestrant; targeted therapies
PMID: 31004402
DOI: 10.1002/cam4.2095
联系客服
