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激素受体（HR）阳性人类表皮生长因子受体2（HER2）阴性乳腺癌的定义为存在雌激素受体和/或孕激素受体，但是不存在HER2基因扩增，大约占全部乳腺癌的65%～70%，其发病率随年龄增长而增加，其治疗方法因不同分期而不同。内分泌治疗是早期和晚期HR阳性HER2阴性乳腺癌的主要治疗方法，内分泌治疗联合细胞周期蛋白依赖性激酶（CDK）4/6抑制剂可以减少早期HR阳性HER2阴性的远处复发，并提高晚期HR阳性HER2阴性乳腺癌患者的总生存率。根据分期和肿瘤生物学特征，化疗被用于早期HR阳性HER2阴性乳腺癌和晚期HR阳性HER2阴性乳腺癌内分泌治疗耐药后。新型内分泌治疗药物和抗体缀合药物等新的治疗方法正在改变治疗格局。随着新的治疗方案出现，确定最佳治疗顺序对于最大限度提高临床获益同时最大限度降低毒性至关重要。 2023年3月20日，全球影响因子第一神刊、美国癌症学会旗下《临床医师癌症杂志》在线发表美国旧金山加利福尼亚大学海伦迪勒家族综合癌症中心劳拉·于佩尔、霍普·鲁戈等学者的长篇综述：HR阳性HER2阴性早期和晚期乳腺癌的全身治疗。
作者首先讨论了HR阳性HER2阴性乳腺癌的病理学和分子学特征以及内分泌治疗耐药机制，随后讨论了针对HR阳性HER2阴性早期和晚期乳腺癌的现有以及新型疗法，包括基于现有临床研究数据的治疗方案。全文长达36页，参考文献多达234篇。 美国癌症学会旗下《临床医师癌症杂志》每年6期，每期不到10篇文章，其中关于癌症统计的文章每年被引用几千次，故该刊的影响因子一骑绝尘，虽然已从508.702跌至286.130，但是仍然比排名第二的英国《柳叶刀》高出83.399分，故被戏称为神刊。  HR阳性HER2阴性乳腺癌现有内分泌治疗以及靶向治疗联合 此处显示生长因子受体和雌激素受体信号传导通路。当其成员活跃时，这些通路可以促进癌症生长和存活的基因转录。如图所示，内分泌治疗和靶向治疗可以抑制该通路中的步骤。  HR阳性HER2阴性早期乳腺癌现有治疗方案  HR阳性HER2阴性晚期乳腺癌现有治疗方案 CA Cancer J Clin. 2023 Mar 20. IF: 286.130 Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer. Huppert LA, Gumusay O, Idossa D, Rugo HS. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA; Acibadem University, School of Medicine, Istanbul, Turkey; Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA. Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%-70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data. KEYWORDS: breast neoplasms; clinical trials; hormone receptor-positive; hormone therapy; human epidermal growth factor receptor 2 (HER2)-negative breast cancer PMID: 36939293 DOI: 10.3322/caac.21777 |
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