Kaklamani Virginia G, Gradishar William J
Cancer Treatment and Research Center at the University of Texas Health Science Center, San Antonio, Texas, USA.
Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Oncologist. 2017 May;22(5):507-517. doi: 10.1634/theoncologist.2015-0464. Epub 2017 Mar 17.
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. 2017;22:507-517 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.
转移性乳腺癌（MBC）给罹患此病的女性带来了巨大的发病风险和死亡风险。大多数MBC具有激素反应性且雌激素受体呈阳性，这使得内分泌治疗（ET）成为全身治疗的重要组成部分。ET的主要目标是将雌激素对激素反应性MBC的影响降至最低，它是最早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。几种生化机制一直是治疗药物研发的重点，包括选择性雌激素受体调节、芳香化酶抑制和选择性雌激素受体降解。利用这些机制的治疗方法改善了MBC女性患者的生存率和生活质量。然而，在许多情况下，对ET的耐药性限制了其疗效。阐明与ET获得性耐药发展相关的复杂细胞信号级联以及生长因子信号传导与雌激素反应性的相互关系，已将这些途径的组成部分确定为有吸引力的药物研发靶点。基于这些见解并旨在克服激素耐药性，靶向治疗正成为MBC的有效治疗方法。本文综述了MBC的当前内分泌治疗方法，以及近期和正在进行的联合治疗和靶向治疗研究，这些治疗方法通过干扰细胞增殖途径来克服耐药性。2017年；22:507 - 517 对实践的启示：本综述为医学肿瘤学家和其他肿瘤医疗保健提供者提供了对雌激素受体阳性转移性乳腺癌内分泌治疗的基本原理以及现有治疗选择的疗效和安全性概况的当前理解。此外，还讨论了关于治疗耐药性发展的当前概念以及克服耐药性的治疗策略。加强对这些主题的当前信息和理解将有助于临床医生为其患者评估最佳治疗选择。
