晚期激素受体阳性乳腺癌内分泌耐药与靶向治疗药物研究进展

Advances in Endocrine Resistance and Targeted Therapy of Advanced Hormone Receptor-Positive Breast Cancer

激素受体(HR)阳性乳腺癌约占所有乳腺癌的70%,内分泌治疗可使大部分患者获益,但仍有20%~40%的患者可能因内分泌治疗耐药而复发进展。晚期HR阳性乳腺癌内分泌治疗获益可能受基因突变、PI3K-AKT-mTOR等分子通路、细胞周期信号异常活化、表观遗传修饰及肿瘤微环境的影响。自2012年mTOR抑制剂代表药物依维莫司问世以来,内分泌靶向药物研究取得较大进展,抗体药物偶联物、细胞周期蛋白依赖性激酶4/6抑制剂等药物的出现改变了晚期HR阳性乳腺癌患者的治疗格局,极大改善了患者的预后。综述探讨了晚期HR阳性乳腺癌内分泌治疗耐药机制和内分泌分子靶向治疗药物的研究进展,对晚期HR阳性乳腺癌的未来治疗提出新展望。

Hormone receptor(HR)-positive breast cancer accounts for approximately 70%of all breast cancer cases.Endocrine therapy benefits the majority of patients,but still,20%to 40%of patients may experience resistance to endocrine treatment,leading to recurrence and progression of the disease.The efficacy of endocrine therapy in advanced HR-positive breast cancer can be influenced by genetic mutation,molecular pathways such as PI3K-AKT-mTOR,abnormal activation of cell cycle signaling,epigenetic modification,and the tumor microenvironment.Since the introduction of mTOR inhibitors represented by everolimus in 2012,there have been significant advancements in the research of endocrine-targeted therapies.The emergence of such drugs as antibody-drug conjugates and cyclin-dependent kinase 4/6 inhibitors has changed the treatment landscape for advanced HR-positive breast cancer patients,significantly improving patients’prognosis.This article reviews the mechanisms of resistance to endocrine therapy in advanced HR-positive breast cancer and the research progress in endocrine-targeted molecular therapies,in the hope of providing new perspectives on the future treatment of advanced HR-positive breast cancer.