Neurocognitive dysfunction is reported in women with breast cancer even prior to receipt of adjuvant therapy; however, there is little understanding of underlying mechanisms. We tested the hypothesis that pretreatment neurocognitive dysfunction in newly diagnosed patients is related to immunological activation, as indexed by pro-inflammatory cytokines. One hundred seventy-four postmenopausal patients with newly diagnosed breast cancer underwent a comprehensive neuropsychological evaluation (assessment of cognitive function, mood, and fatigue) and measurement of key cytokine levels prior to surgery. Age-matched control participants without cancer were evaluated concurrently. Multivariable regression analyses examined the contribution of circulating Interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and soluble TNF receptor type two (sTNF-RII) in predicting neurocognitive performance in patients after controlling for key factors thought to impact functioning. All tests of statistical significance were two-sided. Memory performance was statistically significantly reduced, in patients compared with controls (P = .02). Of the three cytokines measured, only IL-1ra was statistically significantly elevated in cancer patients when compared with control participants (mean ± SD, 375 ± 239 pg/mL vs 291 ± 169 pg/mL, P = .007). After controlling for age, education, race, mood, fatigue, body mass index, and comorbidity, cytokines independently explained 6.0% of the total variance in memory performance (P = .01) in cancer patients but not control participants, with higher sTNF-RII associated with worse functioning. Exploratory analyses found that comorbidity statistically significantly explained variance in processing speed and executive functioning (P = .03 and P = .03, respectively). An association of TNF with memory, previously reported in patients after exposure to chemotherapy, was found prior to initiation of any treatment, including surgery. This association requires further investigation as sTNF-RII was not higher in cancer patients relative to control participants.

Background: The coronavirus disease 2019 (COVID‐19) pandemic has had wide‐ranging health effects and increased isolation. Older with cancer patients might be especially vulnerable to loneliness and poor mental health during the pandemic.Methods: The authors included active participants enrolled in the longitudinal Thinking and Living With Cancer study of nonmetastatic breast cancer survivors aged 60 to 89 years (n = 262) and matched controls (n = 165) from 5 US regions. Participants completed questionnaires at parent study enrollment and then annually, including a web‐based or telephone COVID‐19 survey, between May 27 and September 11, 2020. Mixed‐effects models were used to examine changes in loneliness (a single item on the Center for Epidemiologic Studies–Depression [CES‐D] scale) from before to during the pandemic in survivors versus controls and to test survivor‐control differences in the associations between changes in loneliness and changes in mental health, including depression (CES‐D, excluding the loneliness item), anxiety (the State‐Trait Anxiety Inventory), and perceived stress (the Perceived Stress Scale). Models were adjusted for age, race, county COVID‐19 death rates, and time between assessments.Results: Loneliness increased from before to during the pandemic (0.211; P = .001), with no survivor‐control differences. Increased loneliness was associated with worsening depression (3.958; P < .001) and anxiety (3.242; P < .001) symptoms and higher stress (1.172; P < .001) during the pandemic, also with no survivor‐control differences.Conclusions: Cancer survivors reported changes in loneliness and mental health similar to those reported by women without cancer. However, both groups reported increased loneliness from before to during the pandemic that was related to worsening mental health, suggesting that screening for loneliness during medical care interactions will be important for identifying all older women at risk for adverse mental health effects of the pandemic.

Neurocognitive sequelae are among the most debilitating late effects experienced by survivors of childhood cancer, with far reaching consequences for educational, social, and adaptive development. Empirically validated interventions to address such disease and treatment related psychosocial morbidities are needed. We conducted a pilot study to evaluate participants' acceptance and impact of a 15-session, clinic-based training program to teach compensatory learning and problem-solving skills in survivors with cognitive deficits. The intervention program consisted of 5 core components designed to improve daily problem solving, attention and memory, and academic performance. A sample of 12 survivors completed the program. Virtually all objective performance scores showed gains from preintervention to postintervention in the expected positive direction, although only 2 of the gains were statistically significant. Parent responses indicated they perceived the skills taught to be useful, to have improved the child's problem-solving ability and learning skills, to have provided concrete and practical interventions for the home, and to have increased parental knowledge. Similarly, the children rated the overall program high, and reported satisfaction with learning more about their relative cognitive strengths and weaknesses and practical problem solving for academic difficulties. Although the majority of enrolled families completed at least 70% of the training sessions, the overall low participation rate from eligible families raise concern about widespread acceptance of such programs in the oncology clinic. The limitations of the study design and recommendations for future research are discussed.

We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls. Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls. Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05). Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.