2024年改变晚期乳腺癌临床实践的重要研究进展

doi:10.19401/j.cnki.1007-3639.2025.02.005

摘要/Abstract

摘要：

随着分子生物学研究的深入和精准医学的发展，晚期乳腺癌的治疗手段日益丰富。2024年，不同分子亚型晚期乳腺癌治疗领域的多项研究均取得了进展。其中，内分泌治疗联合细胞周期蛋白依赖性激酶4和6（cyclin-dependent kinase 4/6，CDK4/6）抑制剂已成为激素受体阳性晚期乳腺癌的一线标准治疗方案。氟维司群联合阿贝西利可作为CDK4/6抑制剂治疗失败后的治疗选择。而对于伴有AKT信号转导通路异常的患者，氟维司群联合AKT抑制剂capivasertib可为患者带来显著的远期生存获益。德曲妥珠单抗（trastuzumab deruxtecan，T-DXd）则为人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）超低表达人群提供了新的治疗选择。对于HER2阳性晚期乳腺癌，紫杉类药物联合曲妥珠单抗与帕妥珠单抗或吡咯替尼仍是目前曲妥珠单抗敏感人群的标准一线治疗方案。DESTINY-Breast07研究评估了T-DXd用于一线治疗的可行性，结果显示，无论是单药或联合帕妥珠单抗，其无进展生存率（progression-free survival，PFS）均不劣于既往研究中的标准治疗方案。针对HER2阳性脑转移患者，PERMEATE研究的更新数据显示，吡咯替尼联合卡培他滨方案可带来总生存期获益。DESTINY-Breast12研究表明，T-DXd对全身和颅内病灶的抗肿瘤活性相似，可作为HER2阳性脑转移患者的有效治疗选择。晚期三阴性乳腺癌（triple-negative advanced breast cancer，TNBC）的治疗策略正在从传统化疗转向以化疗联合免疫治疗以及抗体药物偶联物（antibody-drug conjugate，ADC）为主的治疗模式。TORCHLIGHT研究显示，化疗联合免疫检查点抑制剂特瑞普利单抗可改善晚期TNBC患者的预后。NCC2167研究表明，当化疗与免疫治疗联合使用时，节拍式化疗相比传统方式具有高疗效及低毒性的特点。本文对上述2024年晚期乳腺癌领域的重要研究进展进行梳理，并结合相关研究数据，总结了晚期乳腺癌患者管理和治疗决策的临床经验，以供同行参考。展望未来，后续临床研究需重点关注患者的个体差异、肿瘤的异质性以及治疗耐药性问题，以提升晚期乳腺癌的治疗效果和患者的生活质量。

关键词: 晚期乳腺癌, 细胞周期蛋白依赖性激酶4/6抑制剂, 抗体药物偶联物, 免疫检查点抑制剂

Abstract:

With advancements in molecular biology research and precision medicine, treatment options for advanced breast cancer have become increasingly diverse. In 2024, significant research progress has been achieved across different molecular subtypes of advanced breast cancer. Endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has become the standard first-line treatment for hormone receptor-positive advanced breast cancer. Fulvestrant combined with abemaciclib serves as a treatment option after failure in CDK4/6 inhibitors. For patients with mutations in the AKT pathway, fulvestrant combined with the AKT inhibitor capivasertib provides significant long-term survival benefits. Trastuzumab deruxtecan (T-DXd) has emerged as a novel treatment option for patients with HER2 ultra-low expression. For HER2-positive advanced breast cancer, taxanes combined with trastuzumab and pertuzumab or pyrotinib remain the standard first-line treatments for trastuzumab-sensitive patients. The DESTINY-Breast07 trial evaluated the feasibility of using T-DXd as a first-line treatment, showing that whether used as monotherapy or in combination with pertuzumab, progression-free survival (PFS) was non-inferior to standard regimens reported in previous studies. For HER2-positive patients with brain metastases, updated results from the PERMEATE trial indicated that the combination of pyrotinib and capecitabine could provide overall survival benefits. The DESTINY-Breast12 trial demonstrated that T-DXd had similar antitumor activity against systemic and intracranial lesions, making it an effective treatment option for HER2-positive patients with brain metastases. Treatment strategies for advanced triple-negative breast cancer (TNBC) are shifting from conventional chemotherapy to regimens centered on chemotherapy combined with immunotherapy and antibody-drug conjugates (ADCs). The TORCHLIGHT trial showed that chemotherapy combined with the immune checkpoint inhibitor toripalimab improved the prognosis of patients with advanced TNBC. The NCC2167 trial found that when chemotherapy was combined with immunotherapy, metronomic chemotherapy offered superior efficacy and lower toxicity compared to conventional approaches. This article reviewed the significant research progress in advanced breast cancer in 2024. By summarizing related research data, it provides insights into the clinical experience of managing and making treatment decisions for patients with advanced breast cancer, serving as a reference for peers. Looking ahead, future clinical research should focus on individual differences among patients, tumor heterogeneity, and treatment resistance, aiming to improve treatment outcomes and the quality of life for patients with advanced breast cancer.

Key words: Advanced breast cancer, Cyclin-dependent kinase 4/6 inhibitors, Antibody-drug conjugate, Immune checkpoint inhibitor

中图分类号:

R737.9

吴淞, 袁洋, 江泽飞. 2024年改变晚期乳腺癌临床实践的重要研究进展[J]. 中国癌症杂志, 2025, 35(2): 186-194.

WU Song, YUAN Yang, JIANG Zefei. Important clinical studies that changed the clinical practice of advanced breast cancer in 2024[J]. China Oncology, 2025, 35(2): 186-194.

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