Abstract Background: For individuals with breast cancer undergoing chemotherapy, a nutritious, protein-rich diet may reduce side effects and improve outcomes. While emerging evidence supports the role of protein in managing cancer-related fatigue, few studies have focused on non-metastatic breast cancer or considered physical activity. This study examined the relationship between protein intake, physical activity, and fatigue in women with Stage I-III breast cancer receiving chemotherapy. Methods: This is a secondary analysis of the Genetics, Molecular Mechanisms, and Symptom Science (GEMMS) study, a longitudinal cohort of women undergoing curative-intent chemotherapy with follow up for 5 years. Protein and total caloric intake were assessed at baseline using the Automated Self-Administered Dietary Assessment (ASA24). Suboptimal protein intake was defined as 0.80 g/kg per the Recommended Dietary Allowance (RDA). Exercise was measured via the Recent Physical Activity Questionnaire (RPAQ) at baseline, and participants were ranked into quartiles. Fatigue was assessed at baseline and the end of chemotherapy using the PROMIS Fatigue Short Form 8a, with a T-score 55 indicating clinically significant fatigue. Linear and logistic regression models evaluated associations between protein intake, exercise, and fatigue post-chemotherapy completion while adjusting for age, stage of cancer, chemotherapy intensity, and baseline fatigue. Results: A total of 95 women, median age 53 years IQR 42-63 were included. Of these, 39% (n = 37) had suboptimal protein intake, with median protein intake of 0.88g/kg IQR 0.60-1.12. The characteristics of women with optimal and suboptimal protein intake are compared in Table 1. At chemotherapy competition, 41% (n = 39) reported clinically significant fatigue. This was numerically higher among women with suboptimal protein intake (43.2% compared to 39.7%) but did not reach statistical significance. In multivariable models, neither protein intake nor exercise were associated with fatigue. Baseline fatigue was the only consistent predictor: for each 1-unit increase in baseline fatigue T-score, the odds of post-treatment fatigue increased by 10% (aOR 1.10; 95% CI 1.03-1.17; p = 0.003). Conclusion: Protein intake and exercise were not significantly associated with fatigue during chemotherapy; however, baseline fatigue was a strong predictor of post-treatment fatigue. Future studies may benefit from exploring the micronutrient composition of dietary intake to discover other contributing factors to chemotherapy fatigue. Citation Format: I. V. Critchfield-Jain, M. A. Fiala, Y. Park, E. Salerno, L. Peterson. Protein Intake, Exercise, and Chemotherapy-Related Fatigue in Women with Breast Cancer 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 PS1-01-30.
Critchfield-Jain et al. (Tue,) studied this question.