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. 2018 Aug;23(8):974-981.
doi: 10.1634/theoncologist.2018-0077. Epub 2018 Jun 22.

Endocrine Therapy in Premenopausal Hormone Receptor Positive/Human Epidermal Growth Receptor 2 Negative Metastatic Breast Cancer: Between Guidelines and Literature

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Endocrine Therapy in Premenopausal Hormone Receptor Positive/Human Epidermal Growth Receptor 2 Negative Metastatic Breast Cancer: Between Guidelines and Literature

Richard Tancredi et al. Oncologist. .
Free PMC article


There is growing interest in the endocrine treatment (ET) of premenopausal women with hormone receptor positive (HR+) metastatic breast cancer (MBC). This review summarizes available data on endocrine therapy for this patient subset and aims to define the most appropriate treatment approach. The combination of luteinizing hormone-releasing hormone (LHRH) agonists plus tamoxifen seems effective and safe and is considered as being superior to either approach alone; still, single-agent therapy remains an acceptable treatment option. Due to their mechanism of action, aromatase inhibitors alone are not suitable for the treatment of premenopausal patients, but the combination with LHRH agonists may result in excellent disease control. Fulvestrant, in conjunction with LHRH agonists, also yields interesting results regarding clinical benefit rate and time to progression; currently, other orally available selective estrogen receptor downregulators are under clinical evaluation. Recently, targeted drugs have been added to ET in order to reverse endocrine resistance, but only limited information regarding their activity in premenopausal patients is available. The cyclin dependent kinase 4 and 6 inhibitor palbociclib when combined with fulvestrant and LHRH agonists was shown to prolong progression-free survival over endocrine therapy alone in pretreated patients; similar results were obtained with the addition of abemacicilib or ribociclib to endocrine therapy. Currently, activity of the mammalian target of rapamycin inhibitor everolimus in combination with letrozole and goserelin is under assessment in premenopausal patients after progression on tamoxifen (MIRACLE trial).

Implications for practice: This review provides clinicians with an overview on the available data regarding endocrine treatment of hormone receptor positive (HR+) metastatic breast cancer (MBC) in premenopausal women and summarizes the treatment options available in routine clinical practice. Knowledge of an up-to-date therapeutic approach in women with premenopausal HR+ MBC will lead to better disease management, thereby improving disease control and quality of life while minimizing side effects.

摘要 绝经前女性激素受体阳性(HR+)转移性乳腺癌(MBC)内分泌治疗(ET)越来越受到关注。本文总结了有关该患者人群内分泌治疗的现有数据,旨在确定最合适的治疗方法。促黄体生成激素释放激素(LHRH)激动剂与他莫昔芬联合使用似乎安全有效,并且被认为优于任何一种单药治疗,然而,单药疗法仍然是一种可接受的治疗选项。由于芳香化酶抑制剂作用机制的原因,单药治疗不适合绝经前期的患者,但与 LHRH 激动剂联合应用可更好地控制疾病。氟维司群与 LHRH 激动剂联合使用,在临床受益率和至进展时间方面也出现了值得关注的结果。目前,其他现有的口服选择性雌激素受体下调调节剂正在接受临床评估。最近,为了逆转内分泌抵抗,已将靶向药物添加到 ET 中,但有关其在绝经前期患者的作用的信息有限。与单纯内分泌治疗相比,将细胞周期蛋白依赖性激酶4和6抑制剂palbociclib与氟维司群和 LHRH 激动剂联合使用,可以延长经治患者的无进展生存期。在内分泌治疗中加入 abemacicilib 或ribociclib也取得了类似的结果。目前正在他莫昔芬经治后进展的绝经前期患者中,评估雷帕霉素抑制剂依维莫司与来曲唑、戈舍瑞林联合应用对哺乳动物靶点的作用(MIRACLE试验)。 实践意义: 本文为临床医生提供了关于绝经前女性激素受体阳性(HR+)转移性乳腺癌(MBC)内分泌治疗(ET)的现有数据概述,并总结了常规临床实践中的治疗方案。了解绝经前HR+的MBC女性最新治疗方法将有助于更好的管理疾病,从而提高疾病控制率和生活质量,同时最大限度地减少副作用。

Keywords: Endocrine therapy; Hormone receptor positive; Metastatic breast cancer; Premenopausal.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.


Figure 1.
Figure 1.
Endocrine therapy for premenopausal women with hormone receptor positive metastatic breast cancer. Abbreviations: AI, aromatase inhibitor; ET, endocrine treatment; OFS, ovarian function suppression; tam, tamoxifen.

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