The concept of “cancer chemotherapy-related cognitive impairment” was first introduced by Silberfarb in 1983 and refers to the altered cognitive function of cancer patients during or after chemotherapy. In other words, chemotherapy decreases cognitive function in cancer patients, also known as “chemo brain”. Currently, cancer chemotherapy-related cognitive impairment has become an important clinical problem, and it seriously affects the quality of life of cancer patients after treatment. ”Cancer-related cognitive impairment (CRCI) is not appropriately referred to as “chemo brain” because the onset of cancer-related cognitive impairment generally precedes the onset of chemotherapy. Therefore, a new concept of “cancer brain” is needed to define cancer-related cognitive impairment according to its mechanism of action for further targeted interventions. Recent research evidence Although the relationship between cognitive function and adjuvant cancer therapy has been previously investigated, no studies have been conducted to assess cognitive function in breast cancer patients prior to treatment. Recently, Prof. Patel’s team at the University Cancer Hospital in Munich, Germany, analyzed the relationship between neurocognitive performance and blood levels of pro-inflammatory factors in newly diagnosed breast cancer patients, and the results were published online in J Natl Cancer Inst. A total of 174 postmenopausal women with breast cancer were included in the study. Patients with newly diagnosed breast cancer had decreased spoken memory and increased plasma IL-1ra levels compared to control women. In addition, patients had elevated plasma sTNF-RII (a marker of TNFa production) levels associated with memory loss. They concluded that upregulation of cancer-induced levels of pro-inflammatory factors, such as TNFa, may impair memory performance in cancer patients. However, they did not study the effects of diet, medication history, and exercise status on memory function, due to study model limitations. Additional research evidence Preclinical (rat or mouse, induced or transplanted tumor models) studies have all shown a causal relationship between tumor development and host cognitive impairment. Tumor-induced cognitive impairment was accompanied by an upregulation of TNFa mRNA expression levels in the hippocampus, although peripheral blood TNFa levels were not elevated. Interestingly, the tumor-bearing mice in this study also showed “depressive-like” behavior and increased stress-related plasma corticosterone levels. From a more specialized perspective, the effect of cancer on cognitive behavior may be only one of the pathological behavioral symptoms (e.g., cognitive impairment, depression, fatigue, nociceptive sensitization, and insomnia) that accompany tumors. Over time, these symptoms tend to develop in a concentrated manner and are accompanied by altered levels of blood inflammatory factors. Preclinical and clinical studies have found that inflammatory stimuli can induce these pathological behaviors. In other words, pathological behavioral symptoms reflect the existence of an evolutionary adaptive dynamic within the organism. Patel’s team adapted their analysis of fatigue and anxiety; they did not include depression or insomnia in the study. However, both of these pathological behaviors are a direct consequence of a cancer diagnosis. Next research should broaden the study of inflammation-related behavioral symptoms beyond a single behavioral symptom (e.g., cognitive impairment) in order to clarify whether these interacting vegetative nervous system symptoms have different biological mechanisms of action. Cancer-related stress as a psychological process Recent studies have found that differences in cognitive function between pre-chemotherapy breast cancer patients and control women may be caused by cancer-related post-traumatic stress symptoms. For newly diagnosed cancer patients, the situation of undergoing a staging diagnosis and medical examination and facing treatment options can induce acute psychological stress in patients. These stressors not only affect patients’ performance on neurocognitive tests, but may also activate pro-inflammatory pathways in patients. Indeed, psychological stress may interact with inflammatory pathways to synergistically alter cognitive behavior and other behavioral symptoms. In addition, psychological stress may also directly affect the central nervous system, for example by inhibiting neurogenesis and reducing the volume of the hippocampus, which can be exacerbated by biological changes brought about by cancer or cancer treatment. Therefore, research is still needed to investigate the interplay between cancer-inducing psychological and physiological interactions. Caution is needed in the treatment of cancer-related cognitive impairment. As to how to treat cancer-related cognitive impairment and other pathological behaviors, a peripheral blood TNF sequestration strategy (e.g., infliximab) should be carefully considered because TNF plays an important and complex role in tumor immune surveillance. However, it is possible to start with IL-1 and IL-6 (which can promote Th17 immunity) as they are involved in several processes in neuropathology. Behavioral interventions hold promise for cancer patients and may have the potential to intervene in regulatory pathways between the brain and the immune system. Physical activity can improve cancer-related cognitive impairment Physical activity is known to benefit physical and mental health, for example by improving cognitive performance and brain function in the elderly, alleviating fatigue and depressive symptoms in cancer patients, and reducing levels of inflammatory factors in the body. In addition, physical activity can also enhance the effectiveness of chemotherapy by alleviating tumor hypoxia. In the case of aggressive cancer treatment, physical activity may be even more beneficial. Studies have found that physical activity not only inhibits the triggers for the development of pathological behavioral symptoms (e.g. inflammation), but also alleviates pathological behavioral symptoms with minimal side effect costs. In other words, exercise interventions could directly alter the trajectory of cancer-related cognitive impairment. Of course, this theoretical speculation still needs to be validated by clinical randomized trials. In summary However, it is now clear: tumor cells release pro-inflammatory factors, and activation of the pro-inflammatory factor network alters behavioral symptoms in cancer patients. Understanding the mechanisms involved will help clinical interventions for cancer-related symptoms and improve the quality of patient survival.