Anti-oestrogen-based therapies, often combined with a CDK4/6 inhibitor, are the current standard-of-care first-line therapy for patients with advanced-stage hormone receptor-positive (HR⁺) breast cancer. Resistance to anti-oestrogen agents inevitably occurs, mediated by oestrogen receptor (ER)-dependent or ER-independent mechanisms that drive tumour progression. Emerging endocrine therapies include, but are not limited to, next-generation oral ER degraders and proteolysis targeting chimeras, which might be particularly effective in patients with ESR1-mutant breast cancer. Furthermore, cancers harbouring driver alterations in oncogenic signalling pathways, including AKT and PI3K, might be susceptible to novel combination strategies involving targeted inhibitors. Next-generation CDK2/4 inhibitors are an area of active clinical investigation, and efforts are ongoing to evaluate the role of sequential CDK inhibition. Approved and emerging antibody–drug conjugates exploiting novel target antigens have also demonstrated promising clinical activity. These novel agents, as well as further identification and characterization of predictive biomarkers, will hopefully continue to improve clinical outcomes, reduce the incidence of toxicities, and limit the extent of overtreatment in this population. In this Review, we describe the evolving treatment paradigm for patients with metastatic HR⁺ breast cancer in light of the growing armamentarium of drugs and biomarkers that will help to shape the future therapeutic landscape. These strategies are expected to involve tumour molecular profiling to enable the delivery of precision medicine.

基于抗雌激素的疗法通常与 CDK4/6 抑制剂联合使用，是目前晚期激素受体阳性 (HR ⁺ ) 乳腺癌患者的标准一线疗法。对抗雌激素药物的耐药性不可避免地会发生，这是由雌激素受体（ER）依赖性或非 ER 依赖性驱动肿瘤进展的机制介导的。新兴的内分泌疗法包括但不限于下一代口服 ER 降解剂和靶向嵌合体的蛋白水解，这可能对ESR1突变乳腺癌患者特别有效。此外，包含 AKT 和 PI3K 等致癌信号通路驱动改变的癌症可能容易受到涉及靶向抑制剂的新型组合策略的影响。下一代 CDK2/4 抑制剂是一个活跃的临床研究领域，并且正在努力评估序贯 CDK 抑制的作用。已批准和新兴的利用新型靶抗原的抗体药物偶联物也表现出了有希望的临床活性。这些新型药物以及预测生物标志物的进一步鉴定和表征将有望继续改善临床结果，降低毒性发生率，并限制该人群过度治疗的程度。在这篇综述中，我们根据不断增长的药物和生物标记物描述了转移性 HR ⁺乳腺癌患者不断发展的治疗模式，这将有助于塑造未来的治疗前景。这些策略预计将涉及肿瘤分子分析，以实现精准医疗。