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. 2026 Feb;35(2):e70411.
doi: 10.1002/pon.70411.

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

Jared D Smith  1 , Alexis C Wardell  2 , Kirsten A Nyrop  2   3 , Allison M Deal  2 , Hyman B Muss  2   3 , Zev M Nakamura  2   4
Affiliations

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

Jared D Smith et al. Psychooncology. 2026 Feb.

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.

Keywords: anxiety; breast cancer; cancer; cognition; depression; fatigue; oncology.

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References

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