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关于推进乳腺癌治疗的叙述性综述:利用PD-1/PD-L1抑制剂的力量改善患者预后

Narrative review on advancing breast cancer treatment: harnessing the power of PD-1/PD-L1 inhibitors for improved patient outcomes.

作者信息

Zhang Fan, Wang Shu-Sen

机构信息

Department of Medical Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

出版信息

Transl Breast Cancer Res. 2023 Sep 22;5:2. doi: 10.21037/tbcr-23-23. eCollection 2024.

Abstract

BACKGROUND AND OBJECTIVE

Cancer immunotherapy has significantly advanced the field of oncology, providing novel therapeutic strategies for various malignancies, including breast cancer. The programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway is pivotal in immune regulation, and its inhibitors have demonstrated therapeutic benefits in diverse tumors. This review aims to critically examine the role, clinical efficacy, safety, and future directions of PD-1/PD-L1 inhibitors in breast cancer treatment, with a focus on pembrolizumab, nivolumab, and tislelizumab, and to elucidate the challenges and prospects in this dynamic field.

METHODS

A comprehensive literature search was conducted, adhering to Narrative Review reporting checklist for transparent reporting. Data from selected studies were qualitatively analyzed to synthesize key findings related to the mechanisms of action, clinical applications, and challenges of PD-1/PD-L1 inhibitors in breast cancer.

KEY CONTENT AND FINDINGS

PD-1 inhibitors have shown remarkable efficacy in various malignancies, including advanced triple-negative breast cancer (TNBC), where they have been investigated both in combination with chemotherapy and as neoadjuvant/adjuvant treatment. The exploration of these inhibitors in other breast cancer subtypes, such as human epidermal growth factor receptor-positive and hormone receptor-positive breast cancer, is ongoing. The review highlights the challenges in patient selection, management of immune-related adverse events (irAEs), and the emergence of resistance mechanisms. It underscores the need for ongoing research focusing on identifying reliable predictive biomarkers, elucidating mechanisms of resistance, and optimizing treatment strategies.

CONCLUSIONS

PD-1/PD-L1 inhibitors hold substantial promise in advancing breast cancer treatment. This review provides critical insights and emphasizes the clinical importance of continued scientific exploration to refine patient selection criteria, improve treatment outcomes, and expand the applications of immunotherapy in breast cancer. Further research is imperative to overcome the existing challenges and realize the full therapeutic potential of these inhibitors in breast cancer and other malignancies.

摘要

背景与目的

癌症免疫疗法显著推动了肿瘤学领域的发展,为包括乳腺癌在内的各种恶性肿瘤提供了新的治疗策略。程序性细胞死亡蛋白1/程序性死亡配体1(PD-1/PD-L1)通路在免疫调节中起关键作用,其抑制剂已在多种肿瘤中显示出治疗益处。本综述旨在批判性地审视PD-1/PD-L1抑制剂在乳腺癌治疗中的作用、临床疗效、安全性及未来方向,重点关注帕博利珠单抗、纳武利尤单抗和替雷利珠单抗,并阐明这一动态领域中的挑战与前景。

方法

遵循叙述性综述报告清单进行全面的文献检索,以实现透明报告。对所选研究的数据进行定性分析,以综合与PD-1/PD-L1抑制剂在乳腺癌中的作用机制、临床应用及挑战相关的关键发现。

关键内容与发现

PD-1抑制剂在包括晚期三阴性乳腺癌(TNBC)在内的各种恶性肿瘤中均显示出显著疗效,在联合化疗以及作为新辅助/辅助治疗方面均有研究。目前正在对这些抑制剂在其他乳腺癌亚型,如人表皮生长因子受体阳性和激素受体阳性乳腺癌中的应用进行探索。该综述强调了患者选择、免疫相关不良事件(irAEs)管理以及耐药机制出现等方面的挑战。强调了持续开展研究以确定可靠的预测生物标志物、阐明耐药机制并优化治疗策略的必要性。

结论

PD-1/PD-L1抑制剂在推进乳腺癌治疗方面具有巨大潜力。本综述提供了关键见解,并强调了持续进行科学探索以完善患者选择标准、改善治疗结果以及扩大免疫疗法在乳腺癌中的应用的临床重要性。必须进一步开展研究以克服现有挑战,并实现这些抑制剂在乳腺癌和其他恶性肿瘤中的全部治疗潜力。

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