Background/Objectives: Cancer-related cognitive impairment (CRCI) is a frequent and clinically significant consequence of breast cancer (BC) and its treatments. With rapidly evolving therapeutics and a growing body of biomarker research, a BC-specific synthesis is needed. This review aimed to evaluate associations between blood- and saliva-based biomarkers and objective and patient-reported cognitive outcomes in adults with non-metastatic BC, while accounting for treatment modality and assessment timing.Methods: This systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD420251079969). PubMed, Embase, and Web of Science were searched for articles published up until April 2025. Eligible studies included adults with BC that investigated associations between blood and/or saliva biomarkers and cognitive outcomes.Results: A total of 53 studies met inclusion criteria: 31 examined biochemical biomarkers; 17, genetic; and 5, both. Assessments were predominantly post-treatment. Baseline measures were more infrequent. Chemotherapy (ChT) predominated, while endocrine therapy (ET) and radiotherapy (RT) were variably examined. Targeted therapies and immunotherapies were rarely included. IL-6 and TNF-α were most consistently linked to poorer cognition, although results varied by timing and assessment type. CRP and derived indices showed intermittent associations. Stress-axis markers and BDNF were mainly related to subjective outcomes. Genetic findings implicated DNA repair and oxidative stress pathways, while APOE, COMT, and BDNF results were inconsistent.Conclusions: Evidence for biomarker correlates of CRCI in BC is highly heterogeneous. Longitudinal, harmonized, and treatment-specific studies are needed to establish reproducible biomarker panels for risk stratification and targeted intervention.
**背景/目的：** 癌症相关认知障碍（CRCI）是乳腺癌（BC）及其治疗中常见且具有临床意义的后果。随着治疗方法的快速发展和生物标志物研究的不断深入，有必要进行针对乳腺癌的综合分析。本综述旨在评估非转移性乳腺癌成人患者中，基于血液和唾液的生物标志物与客观及患者报告的认知结局之间的关联，同时考虑治疗方式和评估时机。 **方法：** 本系统综述遵循系统综述和荟萃分析首选报告项目（PRISMA）指南，并已在国际前瞻性系统综述注册库（PROSPERO，ID：CRD420251079969）中预注册。检索了截至2025年4月发表的PubMed、Embase和Web of Science文献。符合条件的研究包括调查血液和/或唾液生物标志物与认知结局之间关联的乳腺癌成人患者研究。 **结果：** 共有53项研究符合纳入标准：31项研究检测生化生物标志物；17项研究检测遗传生物标志物；5项研究同时检测两者。评估主要在治疗后进行，基线测量较为少见。化疗（ChT）是主要研究对象，而内分泌治疗（ET）和放射治疗（RT）的研究情况不一。靶向治疗和免疫治疗很少被纳入。IL-6和TNF-α与较差的认知功能关联最为一致，尽管结果因评估时机和类型而异。CRP及其衍生指标显示出间歇性关联。应激轴标志物和BDNF主要与主观结局相关。遗传学发现涉及DNA修复和氧化应激通路，而APOE、COMT和BDNF的结果不一致。 **结论：** 关于乳腺癌CRCI相关生物标志物的证据存在高度异质性。需要进行纵向、标准化和针对特定治疗的研究，以建立可重复的生物标志物组合，用于风险分层和靶向干预。
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