腔面型乳腺癌内分泌治疗耐药的机制与治疗进展

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

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。

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 endocrineresistant 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.