Exercise, vagal regulation, and inflammatory symptom clusters in breast cancer survivors: a structured mini-review and hypothesis-generating framework

Breast cancer survivors frequently experience co-occurring fatigue, sleep disturbance, anxiety, depressive symptoms, and pain. These symptoms may partly reflect a shared psychophysiological state involving autonomic dysregulation, impaired stress recovery, and low-grade inflammatory activity. Exercise is increasingly recommended as a supportive care strategy for cancer-related fatigue and functional recovery, but the psychophysiological mechanisms linking exercise to symptom improvement remain incompletely understood. This structured mini-review proposes a hypothesis-generating framework in which heart rate variability (HRV), particularly vagally mediated indices such as the root mean square of successive differences (RMSSD) and high-frequency HRV (HF-HRV), may represent a candidate indicator of autonomic flexibility linking exercise, inflammatory activity, and symptom clustering in breast cancer survivors. The cholinergic anti-inflammatory pathway and α7 nicotinic acetylcholine receptor (α7nAChR) signaling are discussed as biologically plausible neuroimmune mechanisms, but direct evidence for this pathway in breast cancer survivorship remains limited. Exercise-related changes in HRV may be consistent with improved vagal regulation and inflammatory moderation; however, HRV is influenced by multiple clinical and behavioral confounders, including cancer treatment exposure, medication use, sleep, comorbidities, and baseline fitness. Therefore, HRV should be interpreted as an adjunctive psychophysiological marker rather than as direct evidence of a causal mechanism. Future trials should combine standardized HRV monitoring, inflammatory biomarkers, and validated symptom-cluster outcomes to test whether changes in autonomic regulation mediate the effects of exercise on inflammation and symptom burden in breast cancer survivors.