Psychological distress is involved in CRCI in breast cancer survivors via mediating cytokine levels

Abstract

Background Cancer‐related cognitive impairment (CRCI) is a frequent consequence in breast cancer survivors after chemotherapy and lowers their quality of life (QOL). Psychological distress is frequently experienced by breast cancer survivors. There are currently few studies investigating the role of psychological distress in the genesis of CRCI. Methods In total, 122 breast cancer survivors after standard chemotherapy within a year were recruited and assessed using the Psychological Distress Thermometer (DT). Sixty breast cancer survivors had non‐psychological distress (NPD group) and sixty‐two breast cancer survivors with psychological distress (PD group). The scores of the Mini‐Mental State Examination (MMSE), prospective and retrospective memory (PM and RM) Questionnaire (PRMQ), and Functional Assessment of Cancer Therapy‐General (FACT‐G) and the levels of cytokines including interleukin‐1 beta (IL‐1β), tumor necrosis factor‐alpha (TNF‐α), and interleukin‐4 (IL‐4) were compared between the two groups. Using PROCESS, we investigated whether psychological distress predicted cognitive function based on MMSE through IL‐1β, TNF‐α, and IL‐4. Results The PD group had higher scores on RM, PM, and FACT‐G and lower scores on MMSE than the NPD group (t = −11.357, t = −10.720, t = −15.419, t = 10.162, respectively; p < 0.05). Meanwhile, a higher level of IL‐1β, TNF‐α, and IL‐4 was observed in the PD group than in the NPD group (t = −3.961, t = −3.396, t = −3.269, respectively; p < 0.05). The link between psychological distress and cognitive function as measured by the MMSE was also mediated by IL‐1β, TNF‐α, and IL‐4 (effect size: 26%, 25%, and 24%). Conclusion Breast cancer patients with psychological distress displayed poor cognitive function, poor memory, and inferior quality of life, which was accompanied by higher cytokine levels of IL‐1β, TNF‐α, and IL‐4. This study demonstrated IL‐1β, TNF‐α, and IL‐4 as potential pathways to CRCI in response to ongoing psychological distress, which provided evidence for the involvement of psychological distress in CRCI in breast cancer survivors.

Inflammation at diagnosis and cognitive impairment two years later in breast cancer patients from the Canto-Cog study

“…CRCI has multifactorial causes including depression, anxiety, and fatigue, which are also known to be associated with inflammation [ 42 , 49 – 51 ]. A recent study found that higher psychological distress indirectly predicted worse cognition through higher levels of IL-1β, TNF-α, and IL-4 [ 52 ]. In our study, we did not find a significant association between objective cognitive impairment and depression, anxiety, fatigue and, BMI (results not shown).…”

Cancer related cognitive impairment: a downside of cancer treatment

“…CRCI is documented most thoroughly to date in women with breast cancer (BC), which represents 22% of all cancer survivors in the United States ( 2 ). BC survivors have reported cognitive dysfunction for 5-10 years following treatment with chemotherapy and/or radiation therapy ( 7 , 14 ).…”

“…Known risk factors that increase incidence of CRCI after chemotherapy include non-cancer related comorbidities, anemia, and genetic predisposition ( 24 , 25 ). The proposed mechanisms for chemotherapy-associated CRCI include decreased neurogenesis, axonal degeneration and demyelination, reduction in dendrite volume and length, increased oxidative stress and free radical formation, neuroinflammation, toxicity to CNS progenitor cells, microglia apoptosis, blood brain barrier disruption, brain blood flow alterations, myelin degradation, production of damage associated molecular patterns, cytokine-induced neurotoxicity, reduced glucose metabolism, alteration in brain water content, and fluctuations in neurotransmitter levels ( 5 , 14 , 22 , 23 , 25 , 26 ). Select chemotherapy drugs, including 5-fluorouracil (5-FU), carmustine (BCNU), lomustine (CCNU), temozolomide (TMZ) cross the intact blood brain barrier to directly injure the brain.…”

The Mediating Role of Psychological Resilience in the Relationship Between Spiritual Well-Being and Supportive Care Needs in Women With Breast Cancer

“…Despite the frequent diagnosis of breast cancer, mortality rates have either remained stable or decreased since the 1990s, due to advanced early detection and treatment methods (3). However, breast cancer patients experience varying degrees of psychological distress during both the pre-treatment and posttreatment processes (4). Spirituality, in this context, is an important source of strength and coping for cancer patients to adapt to their illness (5).…”