乳腺癌芳香化酶抑制剂耐药的研究进展

Research progress of resistance to aromatase inhibitor therapy in breast cancer

乳腺癌是女性常见的恶性肿瘤,约70%的患者为雌激素受体(estrogen receptor,ER)和(或)孕激素受体(progesterone receptor,PR)阳性,内分泌治疗是激素受体(hormone receptor,HR)阳性乳腺癌的主要治疗方式之一。近几十年来,内分泌治疗药物不断发展并应用于临床,乳腺癌患者的复发转移风险显著降低,预后得到长足改善。芳香化酶抑制剂(aromatase inhibitor,AI)在乳腺癌内分泌治疗中发挥重要作用,然而绝大部分患者会发生原发性或继发性耐药,因此克服内分泌治疗药物耐药对进一步提高临床疗效至关重要。从遗传学、表观遗传学及细胞内信号转导通路等方面对HR阳性乳腺癌患者AI治疗后耐药的机制及最新的研究进展进行综述,以期为临床诊疗及科研提供参考。

Breast cancer is one of the most common malignancies in women.About 70%of patients are estrogen receptor(ER)and/or progesterone receptor(PR)positive.Endocrine therapy is one of the main treatments for hormone receptor(HR)positive breast cancer.In recent decades,endocrine therapy drugs have been continuously innovated and applied in clinical practice,the risk of recurrence/metastasis of breast cancer patients has been significantly reduced,and the prognosis has been greatly improved.Among them,aromatase inhibitors(AIs)play an important role in endocrine therapy for breast cancer.However,a large number of patients develop either primary or secondary endocrine therapy drug resistance.Therefore,it is very important to overcome endocrine therapy drug resistance to further improve clinical efficacy.This article reviewed the mechanisms and the latest research progress of drug resistance in HR-positive breast cancer after prior AI therapy from the aspects of genetics,epigenetics and intracellular signal transduction pathways,so as to provide some guidance for clinical diagnosis,treatment and scientific research.