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Investigate associations between neurobehavioral symptoms during chemotherapy and long-term cognitive impairment in breast cancer survivors.

February 21, 2026

Associations Between Neurobehavioral Symptoms During Breast Cancer Chemotherapy and Patient‐Reported Cognitive Impairment 3 or More Years After Chemotherapy

Key Points

Investigate associations between neurobehavioral symptoms during chemotherapy and long-term cognitive impairment in breast cancer survivors.
Secondary analysis of clinical trial participants with stage I-III breast cancer.
Assessment of cognitive impairment using FACT-Cog PCI at least 3 years post-chemotherapy.
Multivariable log-binomial regression models adjusted for age, race, and education.
39% of participants reported cognitive impairment at an average of 6 years post-chemotherapy.
Increased risk of cognitive impairment associated with moderate or worse depression (RR 1.75), anxiety (RR 1.95), and fatigue (RR 1.92) during chemotherapy.
Sensitivity analyses showed higher risks of cognitive impairment in patients with mild or no symptoms before chemotherapy.

Abstract

ABSTRACT Background Many patients with breast cancer report cognitive impairment for several years after treatment. The objective of this study was to describe associations between neurobehavioral symptoms experienced during chemotherapy for early‐stage breast cancer and patient‐reported cancer‐related cognitive impairment (CRCI) ≥ 3 years post‐chemotherapy. Methods This study is a secondary analysis of women with stage I‐III breast cancer who had enrolled in clinical trials promoting self‐directed walking during chemotherapy and were re‐consented for a study focused on quality‐of‐life outcomes ≥ 3 years post‐chemotherapy. Patient‐reported CRCI was assessed using the FACT‐Cog PCI (cut point for impairment < 54). Multivariable log‐binomial regression models, adjusting for age, race, and education, examined associations between long‐term CRCI and baseline demographic characteristics, cancer diagnosis and treatment, and patient‐reported neurobehavioral symptoms during chemotherapy and at long‐term follow‐up. Results Among 104 participants, 39% reported CRCI at long‐term follow‐up, on average 6 years post‐chemotherapy range: 2.9–8.8. CRCI was more common among those reporting moderate or worse depressive (RR 1.75, 95% CI 1.11–2.75, p = 0.02), anxiety (RR 1.95, 95% CI 1.22–3.11, p = 0.005), or fatigue (RR 1.92, 95% CI 1.09–3.36, p = 0.02) symptoms during chemotherapy. In sensitivity analyses limited to patients with none or mild symptoms prior to chemotherapy, depressive (RR 2.11, 95% CI 1.23–3.63, p = 0.007) and fatigue (RR 1.81, 95% CI 1.81, 95% CI 1.01–3.24, p = 0.05) symptoms emerging during chemotherapy were also associated with CRCI at follow‐up. Conclusions Patient‐reported neurobehavioral symptoms experienced during chemotherapy, including depression, anxiety, and fatigue, were associated with patient‐reported CRCI years after primary treatment and should be monitored for timely intervention opportunities.

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Associations Between Neurobehavioral Symptoms During Breast Cancer Chemotherapy and Patient‐Reported Cognitive Impairment 3 or More Years After Chemotherapy

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