The University of Liverpool, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, Liverpool L69 3GA, UK; Liverpool & Merseyside Breast Academic Unit, The Linda McCartney Centre, Royal Liverpool University Hospital, Liverpool L7 8XP, UK; Academic Department of Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Wiral CH63 4JY, UK.
Department of Surgery, Imperial College Healthcare NHS Trust, Fulham Palace Road, London W6 8RF, UK.
Mol Cell Endocrinol. 2014 Jan 25;382(1):695-723. doi: 10.1016/j.mce.2013.08.001. Epub 2013 Aug 7.
Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.
内分泌治疗是治疗雌激素受体阳性乳腺癌的主要方法之一。常规使用 5 年的辅助他莫昔芬已经提高了早期乳腺癌的生存率，最近在绝经后环境中发展为包括芳香酶抑制剂。辅助内分泌治疗的最佳持续时间仍然是临床研究的活跃领域，最近的数据支持辅助他莫昔芬使用 10 年而不是 5 年。然而，内分泌治疗受到耐药性的发展的限制，这可能通过多种可能的机制发生，并且已经进行了许多研究，将内分泌治疗与调节这些机制的药物联合使用，旨在预防或延迟耐药性的出现。最近关于哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂依维莫司与内分泌治疗联合使用的试验数据导致了转移性疾病临床治疗途径的重新定义。本文详细介绍了在早期和晚期疾病中使用的当前内分泌治疗方法，以及探索调节耐药途径的潜在新靶点，以及旨在调节肾上腺源性甾体生成激素的药物。
