Mechanisms of Neurotoxic Symptoms as a Result of Breast Cancer and Its Treatment: Considerations on the Contribution of Stress, Inflammation, and Cellular Bioenergetics

PURPOSE OF REVIEW Breast cancer and its treatment are associated with a range of neurotoxic symptoms, such as fatigue, cognitive impairment, and pain. Although these symptoms generally subside after treatment completion, they become chronic in a significant subset of patients. We here summarize recent findings on neuroinflammation, stress, and mitochondrial dysfunction as mechanistic pathways leading to neurotoxic symptom experience in breast cancer patients and survivors. RECENT FINDINGS Neuroinflammation related to stress or cancer treatment and stress resulting from diagnosis, treatment, or (cancer-related) worrying are important predictors of a neurotoxic symptom experience, both during and after treatment for breast cancer. Both inflammation and stress hormones, as well as cancer treatment, can induce mitochondrial dysfunction resulting in reduced cellular energy. SUMMARY We propose reduced cellular energy (mitochondrial dysfunction) induced by inflammation, oxygen radical production, and stress as a result of cancer and/or cancer treatment as a final mechanism underlying neurotoxic symptoms.