乳腺癌是世界上最常见的侵袭性恶性肿瘤，当今有数百万幸存者。 2 型糖尿病 (T2DM) 也是一种全球流行的疾病，也是广泛研究的乳腺癌危险因素。大多数乳腺肿瘤表达雌激素受体，并采用旨在破坏雌激素依赖性信号传导的全身疗法进行治疗。自六年前靶向内分泌治疗出现以来，乳腺癌的死亡率稳步下降。然而，在过去十年中，据报道乳腺癌治疗后患 T2DM 的风险升高，特别是对于接受内分泌治疗的患者。在这篇综述中，我们重点介绍内分泌治疗历史上的关键事件，从他莫昔芬的开发开始。我们还总结了已报道的不良代谢影响的顺序，包括血脂异常、肝脂肪变性和糖耐量受损。我们讨论了根据流行病学数据确定乳腺癌治疗在 T2DM 发展中因果作用的局限性，并描述了信息丰富的临床前研究，这些研究表明内分泌治疗可能通过复杂机制驱动 T2DM 风险和进展。我们还强调了内分泌治疗的挽救生命的益处，并强调需要更好的 T2DM 风险预测生物标志物以及针对不断增长的乳腺癌幸存者群体的预防策略。© 2023。Springer Nature Limited。

Breast cancer is the most common invasive malignancy in the world, with millions of survivors living today. Type 2 diabetes mellitus (T2DM) is also a globally prevalent disease that is a widely studied risk factor for breast cancer. Most breast tumours express the oestrogen receptor and are treated with systemic therapies designed to disrupt oestrogen-dependent signalling. Since the advent of targeted endocrine therapy six decades ago, the mortality from breast cancer has steadily declined; however, during the past decade, an elevated risk of T2DM after breast cancer treatment has been reported, particularly for those who received endocrine therapy. In this Review, we highlight key events in the history of endocrine therapies, beginning with the development of tamoxifen. We also summarize the sequence of reported adverse metabolic effects, which include dyslipidaemia, hepatic steatosis and impaired glucose tolerance. We discuss the limitations of determining a causal role for breast cancer treatments in T2DM development from epidemiological data and describe informative preclinical studies that suggest complex mechanisms through which endocrine therapy might drive T2DM risk and progression. We also reinforce the life-saving benefits of endocrine therapy and highlight the need for better predictive biomarkers of T2DM risk and preventive strategies for the growing population of breast cancer survivors.© 2023. Springer Nature Limited.