Until recently, the standard of care for hormone receptor-positive (HR+) breast cancer was single-agent endocrine therapy, which aims to prevent estrogen receptor signaling. This therapeutic strategy has extended survival without the toxicity associated with chemotherapy, but primary endocrine therapy resistance is common, and secondary resistance develops over time. Adjunct downstream inhibition of the cyclin-dependent kinase (CDK)4/6 pathway, intended to delay and prevent endocrine therapy resistance, has further extended progression-free survival in patients receiving endocrine therapy; however, resistance still eventually develops in these patients. Addition of phosphatidylinositol-3 kinase (PI3K) or mammalian target of rapamycin (mTOR) inhibitors to combined CDK4/6 and endocrine inhibitor regimens may help prolong CDK4/6 inhibitor sensitivity. Early trials combining CDK4/6 inhibitors, PI3K or mTOR inhibitors, and endocrine therapy have shown encouraging signs of clinical activity. However, further research is needed to help understand the extent of treatment benefit from triplet therapy and where this strategy will fit in the treatment sequence for patients with HR+ breast cancer.

中文翻译：

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激素受体阳性，HER2阴性晚期乳腺癌的下一个治疗时代：基于三联体的内分泌疗法。

直到最近，激素受体阳性（HR +）乳腺癌的治疗标准仍是单药内分泌疗法，该疗法旨在预防雌激素受体信号传导。这种治疗策略可以延长生存期，而不会产生化学疗法带来的毒性，但是原发性内分泌治疗耐药性很普遍，继发性耐药性会随着时间而发展。下游抑制细胞周期蛋白依赖性激酶（CDK）4/6通路的目的是延缓和预防内分泌治疗的耐药性，从而进一步延长了接受内分泌治疗的患者的无进展生存期；然而，这些患者最终仍会产生抗药性。在联合CDK4 / 6和内分泌抑制剂方案中加入磷脂酰肌醇3激酶（PI3K）或哺乳动物雷帕霉素靶标（mTOR）可能有助于延长CDK4 / 6抑制剂的敏感性。结合CDK4 / 6抑制剂，PI3K或mTOR抑制剂以及内分泌治疗的早期试验显示出令人鼓舞的临床活性迹象。但是，需要进一步的研究来帮助了解三联疗法的治疗获益程度，以及该策略在哪些HR +乳腺癌患者的治疗方案中将适用。