Immanuel Hospital Märkische Schweiz, Buckow.
Medical University of Brandenburg Theodor Fontane, Immanuel Campus Rüdersdorf, Rüdersdorf bei Berlin, Germany.
Curr Opin Obstet Gynecol. 2023 Feb 1;35(1):62-66. doi: 10.1097/GCO.0000000000000834. Epub 2022 Nov 7.
Hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer does respond to chemotherapy but can be addressed with a better therapeutic index by using biologically modified endocrine therapy. The most pronounced recent successes were reached by antibody drug conjugates (ADCs).
In early HR+/HER2- disease, adjuvant treatment escalations have taken place for high-risk patients using abemaciclib for the HR+ BRCA- subset and olaparib for HR+ BRCA+ patients. In metastatic spread, among all CDK (cyclin-dependent kinase) 4/6 inhibitors used for first-line therapy, only ribociclib improved overall survival in pre and postmenopausal patients. Palbociclib failed to demonstrate overall survival benefits. New options come up with oral selective oestrogen receptor degraders (SERDs) such as elacestrant, which will replace fulvestrant and is clinically important in combination therapies. ADCs, together with new patient categories such as HER2low or HER3+, enlarge the treatment portfolio and challenge the need of supportive care. The antitrophoblast antigen 2 (TROP2) ADC sacituzumab govitecan improves overall survival in heavily pretreated HR+/HER2- patients by 3.2 months. The best improvement of overall survival was shown bý trastuzumab deruxtecan in less pretreated HER2low (HER2 1+ or HER2 2+/no gene amplification) patients with a gained life span of 6 months.
Real-world data on the sequence of different ADCs with similar payloads are needed to establish best possible treatment algorithms. All these new agents will find their place after CDK4/6 inhibitor-based endocrine combination therapy.
激素受体阳性、人表皮生长因子受体 2 阴性（HR+/HER2-）乳腺癌对化疗有反应，但通过使用生物修饰的内分泌治疗，可以获得更好的治疗指数。最近最显著的成功是通过抗体药物偶联物（ADC）实现的。
在早期 HR+/HER2-疾病中，对于 HR+BRCA-亚组的 abemaciclib 和 HR+BRCA+患者的 olaparib 等高风险患者，辅助治疗进行了升级。在转移性扩散中，在所有用于一线治疗的 CDK（细胞周期蛋白依赖性激酶）4/6 抑制剂中，只有 ribociclib 改善了绝经前和绝经后患者的总生存期。palbociclib 未能显示总生存获益。新的选择出现了口服选择性雌激素受体降解剂（SERD），如 elacestrant，它将取代 fulvestrant，并在联合治疗中具有重要的临床意义。ADC 与新的患者类别（如 HER2 低或 HER3+）一起扩大了治疗组合，并挑战了支持性护理的需求。抗滋养层抗原 2（TROP2）ADC sacituzumab govitecan 使大量预处理 HR+/HER2-患者的总生存期延长了 3.2 个月。在预处理较少的 HER2 低（HER2 1+或 HER2 2+/无基因扩增）患者中，trastuzumab deruxtecan 显示出最佳的总生存期改善，生存期延长了 6 个月。
需要真实世界数据来建立最佳的治疗算法，这些数据涉及具有相似有效载荷的不同 ADC 的顺序。所有这些新药物都将在 CDK4/6 抑制剂为基础的内分泌联合治疗之后找到自己的位置。
