Breast cancer is the most frequently diagnosed cancer in women, with estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers diagnosed. Given the dependence on active ER signaling in these tumors, the predominant treatment strategy has been to inhibit various aspects of this pathway including directly antagonizing ER with the use of selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs). Interestingly, the dependence on ER for breast cancer growth is often retained even after progression through several lines of antiestrogen therapy, making ER a bonafide biomarker for this cancer subtype and driving the continued research and development of novel ER-targeted therapeutics to treat this patient population. This, combined with the continuous discovery of mechanisms underlying endocrine resistance, is resulting in a continually evolving treatment landscape for ER+ breast cancer. This review discusses various ER antagonists investigated for the treatment of breast cancer, outlining their pharmacological and tissue-specific mechanisms of action as well as their specified use within the ER+ breast cancer setting. In addition, mechanisms of resistance to SERMs and SERDs, the use of ER antagonists in combination therapy strategies, and the ongoing development of novel drugs are also reviewed in the context of the changing clinical landscape of ER+ breast cancer. Lastly, the role of SERMs and SERDs in non-breast cancer indications is also discussed.

乳腺癌是女性中最常被诊断出的癌症，雌激素受体阳性（ER +）乳腺癌约占诊断出的所有乳腺癌的75％。考虑到这些肿瘤中对活性ER信号的依赖性，主要的治疗策略是抑制该途径的各个方面，包括使用选择性雌激素受体调节剂（SERM）和选择性雌激素受体降解剂（SERD）直接拮抗ER。有趣的是，即使经过几行抗雌激素治疗后，ER仍对乳腺癌的生长依存性，这使ER成为该癌症亚型的可靠生物标志物，并推动了针对该患者人群的新型针对ER的疗法的持续研究和开发。 。这个，结合不断发现内分泌抗性的潜在机制，导致ER +乳腺癌的治疗格局不断发展。这篇综述讨论了为治疗乳腺癌而研究的各种ER拮抗剂，概述了它们的药理和组织特异性作用机制，以及它们在ER +乳腺癌环境中的特定用途。此外，在ER +乳腺癌的临床环境不断变化的背景下，还对SERMs和SERDs的耐药机制，ER拮抗剂在联合治疗策略中的应用以及新药的不断开发进行了综述。最后，还讨论了SERM和SERD在非乳腺癌适应症中的作用。这篇综述讨论了为治疗乳腺癌而研究的各种ER拮抗剂，概述了它们的药理和组织特异性作用机制，以及它们在ER +乳腺癌环境中的特定用途。此外，在ER +乳腺癌的临床环境不断变化的背景下，还对SERMs和SERDs的耐药机制，ER拮抗剂在联合治疗策略中的应用以及新药的不断开发进行了综述。最后，还讨论了SERM和SERD在非乳腺癌适应症中的作用。这篇综述讨论了为治疗乳腺癌而研究的各种ER拮抗剂，概述了它们的药理和组织特异性作用机制，以及它们在ER +乳腺癌环境中的特定用途。此外，在ER +乳腺癌的临床环境不断变化的背景下，还对SERMs和SERDs的耐药机制，ER拮抗剂在联合治疗策略中的应用以及新药的不断开发进行了综述。最后，还讨论了SERM和SERD在非乳腺癌适应症中的作用。对SERM和SERD耐药的机制，ER拮抗剂在联合治疗策略中的应用以及新药的不断开发也在ER +乳腺癌临床环境不断变化的背景下进行了综述。最后，还讨论了SERM和SERD在非乳腺癌适应症中的作用。对SERM和SERD耐药的机制，ER拮抗剂在联合治疗策略中的应用以及新药的不断开发也在ER +乳腺癌临床环境不断变化的背景下进行了综述。最后，还讨论了SERM和SERD在非乳腺癌适应症中的作用。