Biological mechanisms of cancer-related fatigue in breast cancer survivors after treatment: a scoping review

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Implications for cancer survivors: 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.

Keywords: Autonomic nervous system; Biomarkers; Cancer-related fatigue; Diet; Hypothalamo-hypophyseal system; Inflammation.