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Fatigue (PDQ®): Supportive care - Health Professional Information [NCI] - Pathogenesis of Fatigue

Except for chemotherapy-induced anemia, the mechanisms responsible for fatigue in people with cancer are not known. Understanding the causes of fatigue in people with cancer is especially challenging because each individual may experience multiple possible causes of fatigue simultaneously. This multifactorial etiologic hypothesis is apparent in the various models that have been proposed for the study of fatigue.[1,2] Energy balance, stress, life demands, sleep, neurophysiologic changes, disruption of circadian rhythms, cardiac issues, and neuroimmunologic changes are generally incorporated in these models, based on the rationale that these factors are associated with fatigue in contexts other than cancer.[3] The cancer literature supports some of these variables.

There is a burgeoning amount of evidence, particularly in women with breast cancer and men with prostate cancer, that fatigue is associated with markers of increased immune inflammatory activity. When fatigued individuals with a history of breast cancer are compared with breast cancer survivors without fatigue, different patterns emerge with respect to interleukin-6, interleukin-1 receptor antagonist, C-reactive protein, neopterin, and soluble tumor necrosis factor receptor-II.[4,5,6] Although the precise relationships—and the clinical meaning of those relationships—are not yet known, increased cytokines likely contribute to the symptoms of asthenia, fatigue, and lethargy, as supported in animal models of cytokine-induced sickness behavior [7,8] and in humans.[9] There have not yet been large, well-controlled studies that have evaluated the effects of general anti-inflammatory agents on fatigue or cytokine biomarkers.

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Good communication between patients, family caregivers, and the health care team is very important in cancer care. Good communication between patients with cancer, family caregivers, and the health care team helps improve patients' well-being and quality of life. Communicating about concerns and decision making is important during all phases of treatment and supportive care for cancer. The goals of good communication in cancer care are to: Build a trusting relationship between the patient,...

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Other studies demonstrate a change in the regulation of cortisol by the hypothalamic pituitary adrenal axis. One key study put fatigued and nonfatigued breast cancer survivors through a stress battery in a laboratory setting. Nonfatigued survivors mounted a significant cortisol increase in response to acute stress, while fatigued survivors had a very blunted response.[10] Another study has shown fatigued breast cancer survivors have flattened cortisol slopes, having higher levels of cortisol at the end of the day than do nonfatigued survivors.[11] It is the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis that may account for the prolonged inflammatory cytokine milieu; understanding the body's response to numerous chronic stressors in cancer may help in managing fatigue.

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