Abstract Background: Cancer-related cognitive difficulties (CRCD) is a multifaceted condition associated with various comorbid symptoms, making its management challenging. This study aims to evaluate cumulative symptom burden and its association with subjective and objective CRCD in breast cancer survivors. Method: We analyzed baseline data from a randomized clinical trial for addressing CRCD. The study included women with a history of stage 0-III breast cancer, currently free of oncologic disease, who reported moderate or greater CRCD and insomnia, as indicated by an Insomnia Severity Index score≥8. Subjective CRCD was assessed using the perceived cognitive impairment subscale from the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog PCI). Objective CRCD was measured using the normed delayed T score from the Hopkins Verbal Learning Test—Revised (HVLT-R). Comorbid insomnia, fatigue, pain, anxiety, and depression were measured using Insomnia Severity Index, Brief Fatigue Inventory, PROMIS-Global pain item, and Hospital Anxiety and Depression Scale. We calculated a Cumulative Symptom Score based on co-morbid symptom severity to evaluate the cumulative symptom burden. Multivariable linear regression models were used to assess the associations between cumulative symptom burden and CRCD, adjusted for clinical and sociodemographic variables. Results: Among the 260 participants, the mean age was 56.6 years (SD 10.4), with 54 (21.0%) identifying as non-white and 26 (10.0%) as Hispanic survivors. The mean FACT-Cog PCI score and HVLT-R delayed T-score was 36.0 (SD 14.0) points and 46.0 (SD 12.7) points, respectively. A high prevalence of moderate to severe comorbid symptoms was observed in this population: fatigue (90%) being the most common, followed by insomnia (70.0%), pain (45.2%), anxiety (35.4%), and depression (11.5%). In multivariate analyses adjusted for age and chemotherapy, a higher Cumulative Symptoms Score was significantly associated with greater subjective CRCD (Coef. = -3.0, 95% CI = -3.6 to -2.4, p0.001). Each comorbid symptom was also correlated with subjective CRCD (all p0.001). However, the Cumulative Symptoms Score was not associated with objective CRCD (Coef. = -0.2, 95% CI = -0.9 to 0.5, p = 0.58); only insomnia had a significant correlation (r = -0.20, p0.001). Conclusion: Higher cumulative symptom burden was associated with subjective perception of cognitive difficulties but not objective cognitive function among breast cancer survivors; however, insomnia was associated with worsened objective functions. Comprehensive symptom management has the potential to improve subjective appraisal of cognitive difficulties; targeted treatment of insomnia has the potential to improve objective cognitive functions in women with breast cancer. Citation Format: X. Li, K. Lampson, K. Liou, Y. Li, Q. Li, T. Ahles, J. Root, J. Mao. Association Between Cumulative Symptom Burden and Cognitive Difficulties Among Breast Cancer Survivors: A Cross-Sectional Study abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-01-24.
Li et al. (Tue,) studied this question.