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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (8): 854-865.doi: 10.12092/j.issn.1009-2501.2023.08.002

• 乳腺癌药物治疗新进展 • 上一篇    下一篇

腔面型乳腺癌内分泌治疗耐药的机制与治疗进展

张胡云龙,朱秀之,金 希,邵志敏   

  1. 复旦大学附属肿瘤医院乳腺外科/复旦大学乳腺癌研究所,复旦大学上海医学院肿瘤学系,上海  200032
  • 收稿日期:2022-09-09 修回日期:2022-10-25 出版日期:2023-08-26 发布日期:2023-08-29
  • 通讯作者: 邵志敏,男,硕士,主任医师,博导,研究方向:乳腺癌基础和临床研究。 E-mail: zhimingshao@fudan.edu.cn
  • 作者简介:张胡云龙,男,博士研究生,研究方向:乳腺癌基础和临床研究。 E-mail: 18301050159@fudan.edu.cn
  • 基金资助:
    上海市卫生健康委员会卫生健康青年人才(2022YQ012);上海市“医苑新星”青年医学人才培养资助计划;国家自然科学基金青年科学基金项目(81902684)

Mechanisms of endocrine-resistance and therapeutic breakthroughs in hormone receptor-positive, HER2-negative breast cancer

ZHANG Huyunlong, ZHU Xiuzhi, JIN Xi, SHAO Zhimin   

  1. Department of Breast Surgery, Fudan University Shanghai Cancer Center/Fudan University Breast Cancer Institute, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 
  • Received:2022-09-09 Revised:2022-10-25 Online:2023-08-26 Published:2023-08-29

摘要: 腔面型乳腺癌约占整体乳腺癌的60%~70%,靶向雌激素信号通路是其重要的治疗策略,而内分泌治疗耐药的腔面型乳腺癌是临床上公认的治疗难点。既往组学和转化性研究提示,内分泌耐药的成因主要包括基因组变异和表观遗传学变异。针对内分泌耐药腔面型乳腺癌,目前临床上已建立囊括多种药物的多线治疗方案。同时,其他新型靶向治疗也逐渐崭露头角,进一步丰富了临床医师的选择。本文将系统性介绍腔面型乳腺癌发生内分泌耐药的机制、发生内分泌耐药后的靶向治疗策略以及未来研究展望。

关键词: 乳腺癌, 雌激素受体, 内分泌治疗耐药, 靶向治疗

Abstract:

Breast cancers that are positive for hormone receptor but negative for human epidermal growth factor receptor 2 (abbreviated as HR+/HER2-) account for approximately 60% of total cases. Targeting estrogen signaling is one of the most important therapeutic strategies for HR+/HER2- breast cancer. However, the management of endocrine-resistant HR+/HER2- breast cancer remains a difficult issue in clinical practice. Previous multi-omic analysis and translational research have identified the mechanisms underlying endocrine-resistance including genomic alteration and abnormal epigenetic modification. To overcome endocrine-resistance, we have established a comprehensive and coherent therapeutic strategy.  In addition, several novel therapies have shown promising efficacy in previous clinical trials and will emerge as alternative options for targeting endocrine-resistant HR+/HER2- breast cancer. In this review, we will introduce the mechanisms of endocrine-resistance, explain the current therapeutic strategy for endocrine-resistant HR+/HER2- breast cancer and discuss the possible targeted therapies in the future.

Key words: breast cancer, estrogen receptor, endocrine-resistance, targeted therapy

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