Date of Award

January 2024

Document Type


Degree Name

Master of Public Health (MPH)


School of Public Health

First Advisor

Melinda L. Irwin

Second Advisor

Brenda Cartmel



Background: The Hormones and Physical Exercise (HOPE) study demonstrated efficacy of exercise in reducing AI-associated arthralgia in breast cancer survivors. Yet, the underlying mechanism for this relationship remains unclear. Prior research among breast cancer survivors highlights improvements in metabolic and inflammatory biomarkers related to exercise. This secondary analysis of HOPE examined the potential role of metabolic and inflammatory biomarkers in mediating the effect of exercise vs. usual care on AI-associated arthralgia.

Methods: Our analysis included 80 participants (42 exercise arm, 38 usual care) enrolled in the HOPE study. The intervention was a year-long exercise program that included both supervised aerobic exercise and strength training. AI-associated arthralgia was measured using the Brief Pain Inventory (BPI) worst pain score. Eleven serum inflammatory and metabolic biomarkers were assessed at baseline, 6 and 12 months (M). We examined the effect of exercise on biomarker changes from baseline to 6M and baseline to 12M by study arm using paired T-tests. We also assessed if the biomarkers were potential mediators of the primary intervention effect on BPI worst pain score at baseline and 12M. We also studied associations between changes in biomarkers and in BPI worst pain score at 12M using unadjusted and adjusted linear regression models, controlling for age, baseline BMI, and randomization.

Results: No significant differences were observed in the average biomarker changes by study arm at 6M or 12M, nor when stratified by weight loss status. Additionally, none of the biomarkers were significantly associated with BPI worst pain scores at baseline or 12M.

Conclusion: In this secondary analysis of a year-long exercise trial among breast cancer survivors, the intervention did not result in changes in inflammatory or metabolic biomarkers. In addition, we did not find evidence that the improvement in AI-associated arthralgia was mediated through these biomarkers. Given this study was a treatment trial, future research focused on exercise and mechanisms preventing AI-associated arthralgia is needed.


This thesis is restricted to Yale network users only. It will be made publicly available on 05/07/2026