García-González David, Medino-Muñoz Juan, Romero-Elías María, García-Foncillas Jesús, Ruiz-Casado Ana
School of Medicine, Universidad Autónoma de Madrid (UAM), 28029, Madrid, Spain.
Library, Hospital Universitario de Fuenlabrada, 28942, Madrid, Spain.
J Cancer Surviv. 2025 Feb;19(1):414-444. doi: 10.1007/s11764-023-01477-z. Epub 2023 Nov 6.
Cancer-related fatigue (CRF) is the most common symptom experienced by cancer survivors. It is a multidimensional symptom affecting physical, emotional, and/or cognitive spheres, different from other types of fatigue. Characteristically is not alleviated by sleep or rest. CRF could have specific features in breast cancer survivors (BCS), because of sex, hormones, and distinct treatments. On the other hand, more than 25% of BCS report persistent CRF for 10 years or more after the diagnosis. The present study aims to recapitulate the knowledge about the biological mechanisms that potentially drive CRF in BCS after treatment.
To answer a broad question, a scoping review methodology was used. Data were collated from three bibliographic databases: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). Studies were selected if they had included more than 20 BCS, after finishing their treatment, fatigue was measured with a quantitative scale and biomarkers were analyzed.
The final database was composed of 1896 records. Sixty-four studies finally met the eligibility criteria. Inflammation (61%), hypothalamic-pituitary-adrenal (HPA) axis dysregulation (14%), autonomic nervous system (ANS) dysfunction (11%), and diet (9%) were the biological pathways most frequently studied. Unfortunately, results from studies about inflammation and HPA axis show many inconsistencies.
More research about the role of ANS dysfunction and diet on the pathogenesis of CRF would be warranted according to the results of the review. There are some fields such as endocannabinoid systems, mitochondrial dysfunction, gut microbiota, and oxidative stress that have been insufficiently explored.
To widen the scope of future research in the physiopathology of CRF, it is necessary to identify mechanisms that would be potentially involved and have been insufficiently explored. Because of the high prevalence of CRF in BCS and the tremendous impact that fatigue has in their quality of life, it is essential to improve the efficacy of the treatments through a good knowledge of the biological basis of CRF.
癌症相关疲劳（CRF）是癌症幸存者最常见的症状。它是一种影响身体、情感和/或认知领域的多维症状，与其他类型的疲劳不同。其特点是睡眠或休息无法缓解。由于性别、激素和独特的治疗方法，CRF在乳腺癌幸存者（BCS）中可能具有特定特征。另一方面，超过25%的BCS报告在诊断后10年或更长时间持续存在CRF。本研究旨在总结有关治疗后BCS中潜在驱动CRF的生物学机制的知识。
为回答一个广泛的问题，采用了范围综述方法。数据来自三个文献数据库：PubMed、Embase和Cochrane对照试验中央注册库（CENTRAL）。如果研究纳入了20多名完成治疗后的BCS，用定量量表测量疲劳并分析生物标志物，则选择这些研究。
最终数据库由1896条记录组成。64项研究最终符合纳入标准。炎症（61%）、下丘脑-垂体-肾上腺（HPA）轴失调（14%）、自主神经系统（ANS）功能障碍（11%）和饮食（9%）是最常研究的生物学途径。不幸的是，关于炎症和HPA轴的研究结果显示出许多不一致之处。
根据综述结果，有必要对ANS功能障碍和饮食在CRF发病机制中的作用进行更多研究。内源性大麻素系统、线粒体功能障碍、肠道微生物群和氧化应激等一些领域尚未得到充分探索。
为扩大未来CRF生理病理学研究的范围，有必要确定可能涉及但尚未得到充分探索的机制。由于CRF在BCS中患病率高，且疲劳对其生活质量有巨大影响，因此通过深入了解CRF的生物学基础来提高治疗效果至关重要。
