肿瘤细胞治疗研究
英文原题:Advances and challenges in biomarker guided management of triple-negative breast cancer in the era of neoadjuvant chemo-immunotherapy.
Advances and challenges in biomarker guided management of triple-negative breast cancer in the era of neoadjuvant chemo-immunotherapy.
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三阴性乳腺癌(TNBC)约占所有乳腺癌的15-20%,其特征为激素受体缺失及HER2扩增阴性。早期TNBC以侵袭性临床行为、高增殖率、早期复发及倾向发生内脏转移为特征,尽管初始对化疗敏感,但长期预后仍较差。新辅助化疗-免疫治疗的出现,将标准化疗与免疫检查点抑制剂(ICIs)联合,显著提高了病理完全缓解(pCR)率,并重塑了早期TNBC的治疗范式。尽管取得了这些进展,仍有相当比例的患者出现残留病灶或复发,凸显了需要更好的生物标志物来指导治疗决策。本综述全面概述了TNBC中当前及新兴的生物标志物,重点关注其在新辅助化疗-免疫治疗时代的作用。已确立的临床标志物,如pCR和残留肿瘤负荷(RCB),对于新辅助治疗后的风险分层仍然至关重要。除此之外,新兴生物标志物,包括TIL(肿瘤浸润淋巴细胞)(TILs)、程序性死亡配体1(PD-L1)、空间免疫分析、循环肿瘤DNA(ctDNA)、微小RNA(miRNAs)以及致癌信号通路(如PI3K/AKT、MAPK、WNT/β-catenin),正在研究中,以探索其在优化患者选择及预测治疗反应或耐药方面的潜力。TNBC的生物学异质性,涵盖肿瘤内在及免疫微环境变异,导致了治疗结局的差异并增加了临床决策的复杂性。
我们讨论了将新兴生物标志物整合到常规临床实践中的挑战,包括标准化、前瞻性验证以及联合预测模型的开发。通过总结当前和正在研究中的生物标志物,本综述旨在帮助临床医生理解生物标志物驱动的策略如何可能优化新辅助治疗、减少不必要的毒性,并最终改善TNBC的长期结局。
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by the absence of hormone receptors and HER2 amplification. Early-stage TNBC is characterized by aggressive clinical behavior, high proliferative rates, early relapses, and a propensity for visceral metastases resulting in poor long-term outcomes despite initial chemosensitivity. The introduction of neoadjuvant chemo-immunotherapy, combining standard chemotherapy with immune checkpoint inhibitors (ICIs), has significantly improved pathological complete response (pCR) rates and has reshaped treatment paradigms in early TNBC. Despite these advances, a substantial proportion of patients still develop residual disease or relapse, underscoring the need for better biomarkers to guide treatment decisions.
This review provides a comprehensive overview of current and emerging biomarkers in TNBC, focusing on their role in the era of neoadjuvant chemo-immunotherapy. Established clinical markers, such as pCR and residual cancer burden (RCB), remain essential for post-neoadjuvant risk stratification. Beyond these, emerging biomarkers, including tumor-infiltrating lymphocytes (TILs), programmed death ligand 1 (PD-L1), spatial immune profiling, circulating tumor DNA (ctDNA), microRNAs (miRNAs), and oncogenic signaling pathways (e.
g. , PI3K/AKT, MAPK, WNT/β-catenin), are under investigation for their potential to refine patient selection and predict response or resistance to therapy. The biological heterogeneity of TNBC, encompassing both tumor-intrinsic and immune microenvironment variations, contributes to differential treatment outcomes and complicates clinical decision-making.
We discuss the challenges of integrating emerging biomarkers into routine clinical practice, including standardization, prospective validation, and development of combined predictive models. By summarizing both current and investigational biomarkers, this review aims to support clinicians in understanding how biomarker-driven strategies may optimize neoadjuvant therapy, reduce unnecessary toxicity, and ultimately improve long-term outcomes in TNBC.
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