Endocrine Therapy in the Current Management of Postmenopausal Estrogen Receptor‐Positive Metastatic Breast Cancer

Metastatic breast cancer (MBC) results in substantial morbidity and mortality for women afflicted with this disease. A majority of MBCs are hormone‐responsive and estrogen receptor‐positive, making endocrine therapy (ET) an integral component of systemic therapy. With a primary goal of minimizing the effects of estrogen on hormone‐responsive MBC, ETs are among the first targeted treatments that aim to inhibit the influence of estrogen receptor activation on tumor proliferation. Several biochemical mechanisms have been the focus of drug development for treatment, including selective estrogen‐receptor modulation, aromatase inhibition, and selective estrogen‐receptor degradation. Treatments that exploit these mechanisms have improved survival and quality of life for women with MBC. However, in many cases, resistance to ET limits their effectiveness. Elucidation of the complex cellular signal cascades involved in the development of acquired resistance to ET and the interrelationship of growth factor signaling and estrogen responsiveness have characterized components of these pathways as attractive targets for drug development. Based on these insights and with the aim of overcoming hormone resistance, targeted therapies are emerging as useful treatments for MBC. This article reviews current endocrine treatments of MBC as well as recent and ongoing study of combination treatments and targeted therapies that interfere with cellular proliferation pathways as means of overcoming resistance. Implications for Practice This review provides medical oncologists and other oncology health care providers with a current understanding of the rationale for endocrine therapy in estrogen receptor‐positive metastatic breast cancer and the efficacy and safety profile of available treatment options. Additionally, current concepts regarding the development of treatment resistance and the treatment strategies for overcoming resistance are discussed. Enhancing the current information and the understanding of these topics will assist clinicians in evaluating optimal treatment options for their patients. 摘要 转移性乳腺癌（MBC）在女性人群中的发病率较高, 大量患者因此死亡。MBC以激素反应性和雌激素受体阳性类型居多, 这就使得内分泌治疗（ET）成为全身治疗中不可或缺的一部分。激素反应性MBC的首要治疗目标是尽可能降低雌激素对肿瘤的影响, 在这一背景下, ET成为首批旨在抑制雌激素受体激活对肿瘤增殖影响的靶向治疗方法之一。治疗药物的开发热点集中于数种生化机制, 包括选择性调节雌激素受体、抑制芳香化酶和选择性降解雌激素受体。基于以上机制的治疗方法改善了MBC女性患者的生存期和生活质量。但在诸多病例中, ET耐药限制了治疗的有效性。现已阐明ET获得性耐药形成过程中涉及的复杂细胞信号级联反应以及生长因子信号传导与雌激素反应性之间的相互关系, 由此确定以上通路的组成因素是药物开发的理想靶点。基于以上深入了解, 兼以克服激素耐药为目的, 靶向治疗正逐渐成为MBC的有效治疗方