Kim Nayoung, Lukong Kiven Erique
Biochemistry, Microbiology and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
Oncol Rev. 2025 Apr 10;19:1564642. doi: 10.3389/or.2025.1564642. eCollection 2025.
Breast cancer is one of the most significant causes of mortality among women and the second most prevalent cancer worldwide. Estrogen receptor (ER)-positive breast cancers are the most common molecular subtype of breast cancer, comprising about 70% of breast carcinoma diagnoses worldwide. Endocrine therapy is the foremost strategy for the treatment of ER-positive breast cancer. In the United States, the Food and Drug Administration (FDA) has approved endocrine therapies for ER-positive breast cancers that include selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators/degraders (SERDs) and aromatase inhibitors (AIs). The approved SERMS, tamoxifen, toremifene and raloxifene, are the gold-standard treatments. The only FDA-approved SERD available for treating ER and hormone-positive breast cancers is fulvestrant, and various generations of AIs, including exemestane, letrozole, and anastrozole, have also received FDA approval. Herein, we review the major FDA-approved SERMs and SERDs for treating ER-positive breast cancer, focusing on their mechanisms of action. We also explore molecular events that contribute to the resistance of these drugs to endocrine therapies and combinational strategies with drugs such as cyclin-dependant kinases 4/6 (CDK4/6) inhibitors in clinical trials to combat endocrine drug resistance.
乳腺癌是女性死亡的最重要原因之一，也是全球第二大常见癌症。雌激素受体（ER）阳性乳腺癌是乳腺癌最常见的分子亚型，约占全球乳腺癌诊断病例的70%。内分泌治疗是ER阳性乳腺癌治疗的首要策略。在美国，食品药品监督管理局（FDA）已批准用于ER阳性乳腺癌的内分泌治疗药物，包括选择性雌激素受体调节剂（SERM）、选择性雌激素受体下调剂/降解剂（SERD）和芳香化酶抑制剂（AI）。已批准的SERM他莫昔芬、托瑞米芬和雷洛昔芬是金标准治疗药物。唯一经FDA批准用于治疗ER和激素阳性乳腺癌的SERD是氟维司群，包括依西美坦、来曲唑和阿那曲唑在内的各代AI也已获得FDA批准。在此，我们综述了FDA批准的用于治疗ER阳性乳腺癌的主要SERM和SERD，重点介绍其作用机制。我们还探讨了导致这些药物对内分泌治疗产生耐药性的分子事件，以及在临床试验中与细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂等药物联合使用以对抗内分泌药物耐药性的策略。
