Cancer-related cognitive impairment (CRCI) is a complex, multifactorial problem affecting breast cancer survivors and is often accompanied by other symptoms that complicate assessment and management. This cross-sectional analysis used enrollment data from a randomized clinical trial to examine how cumulative symptom burden relates to both subjective CRCI and objective CRCI among women previously treated for stage 0–III breast cancer who were currently free of active oncology disease but reported moderate or greater CRCI and insomnia. The primary objective was to quantify the association between a cumulative symptoms index and cognitive outcomes measured by validated subjective and objective tools.
The analysis included 260 participants with a mean age of 56.6 years. Demographic distribution in the sample included 21% non-White participants and 10% Hispanic participants. Subjective cognitive complaints were measured using the Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog). Objective cognitive performance was assessed with the Hopkins Verbal Learning Test–Revised (HVLT). Co-occurring symptom domains—insomnia, fatigue, pain, anxiety, and depression—were measured by validated self-report instruments described in the trial enrollment data.
To quantify overall symptom burden, investigators calculated a Cumulative Symptoms Score (CSS) that aggregated the presence and/or severity of the five comorbid symptoms (insomnia, fatigue, pain, anxiety, depression). Reported prevalence in this cohort was notable: fatigue affected 90% of participants, insomnia 70%, pain 45%, anxiety 35%, and depression 12%.
Associations between symptom burden and cognitive outcomes were examined using multivariable linear regression models. Models adjusted for key covariates, including age and prior chemotherapy exposure. Correlation analyses were also used to examine relationships between individual symptoms and objective cognitive test scores.
Higher CSS was significantly associated with worse subjective cognitive function as measured by the FACT-Cog. After adjustment for covariates including age and chemotherapy, the CSS demonstrated a coefficient of −3.0 (95% CI −3.6 to −2.4; p < 0.001), indicating that greater cumulative symptom burden related to poorer patient-reported cognitive function. Additionally, each individual comorbid symptom (insomnia, fatigue, pain, anxiety, depression) was correlated with worse subjective CRCI (all p < 0.001), underscoring the contribution of multiple coexistent symptoms to patients’ cognitive complaints.
In contrast to the subjective findings, the overall CSS was not associated with objective cognitive performance on the HVLT (p = 0.58). However, among the individual symptoms, insomnia showed a modest but statistically significant correlation with HVLT scores (r = −0.20; p < 0.001), suggesting that sleep disturbance may uniquely relate to objective memory performance in this cohort.
The analysis indicates a divergence between subjective and objective measures of CRCI in relation to cumulative symptom burden. Higher aggregated symptom burden is strongly associated with worse patient-reported cognitive function, but not with performance on a standard verbal learning test, with the exception of an association between insomnia and HVLT performance. Clinically, these findings suggest that addressing comorbid symptoms through comprehensive symptom management could improve survivors’ subjective experience of cognitive impairment. The link between sleep disturbance and objective memory testing highlights sleep as a potential therapeutic target where intervention might influence both subjective and objective domains.
The trial enrollment data used for this analysis were approved by the Memorial Sloan Kettering Cancer Center institutional review board (IRB number: 20–124). Conflicts of interest were reported for some authors and are detailed in the source; specific disclosures included grants and commercial affiliations for named investigators. All other authors declared no competing interests.
The source provides a concise abstract reporting design, measures, and principal findings; however, detailed descriptions of the CSS construction, the specific self-report instruments used for each symptom, timing relative to cancer treatment, and other methodological specifics are not provided in the abstract. Where additional methodological detail or secondary analyses may be relevant, the abstract does not report them.
In this cohort of breast cancer survivors reporting cognitive complaints and insomnia, greater cumulative symptom burden was associated with worse subjective CRCI but not with global objective memory scores on the HVLT; insomnia correlated with objective performance. The authors propose that comprehensive symptom management may improve how survivors appraise their cognitive function, and that targeting sleep disturbance may be a promising strategy to influence objective cognitive outcomes. These conclusions are derived from the enrollment data analysis reported in the source.