Abstract PS1-05-23: Using Exercise to Improve Arthralgia and Aromatase Inhibitor Adherence in Older Breast Cancer Survivors: Preliminary Results from a Pilot Randomized Controlled Trial

Abstract Background: Aromatase inhibitors (AIs) reduce recurrence and mortality risk in estrogen receptor-positive female breast cancer survivors (BCS), the majority of whom are aged ≥60. However, up to 70% of users discontinue AIs before the recommended duration of therapy, often due to arthralgia, which affects more than 50% of AI users. Despite its prevalence, AI-associated joint pain remains poorly understood, particularly in older survivors. Physical activity (PA) and education may mitigate symptoms and support adherence, yet tailored interventions for this population are lacking. Methods: We tested REJOIN (Relieving Joint Pain and Improving AI Adherence in Older Breast Cancer Survivors), a remotely delivered, supervised exercise and education intervention. We recruited through two sites (Penn State Cancer Institute and Atrium Health Wake Forest Baptist Comprehensive Cancer Center). The pilot randomized controlled trial (RCT) assessed feasibility and early evidence of benefit. Participants (n=24 BCS) received a 16-week, program including resistance and aerobic training, education on AI-related side effects, and self-management strategies. Joint pain was measured via the Brief Pain Inventory (BPI), and AI adherence via the Morisky-Levine Medication Adherence Scale at baseline, 4, 6 and 12 months. Additional measures included physical activity (collected via Actigraph triaxial research-grade accelerometer), modified geriatric assessment battery and a fasting blood draw. Descriptive statistics were calculated for each outcome at baseline, 4 months and the change in-between the two time points to assess effects from the intervention. Between group differences in change were assessed using the Wilcoxon rank-sum test and within-group changes using the Wilcoxon signed-rank test (α=0.05). Effect sizes were calculated using Cohen's d with corresponding 95% confidence intervals to estimate magnitude of changes within and between groups; values of d≥0.5 indicate moderate or greater practical significance. Results: Participants' mean age was 72 years (range 60-88), included >33% from rural areas, and we had 80% retention over the 12 month pilot study. Our study revealed a moderate reduction in joint pain interference (d = -0.465, p=0.43) and a practically significant increase in AI adherence (d = 0.632, p=0.22) from baseline to 4-months post-intervention compared to standard care. From this pilot, we also determined that the exercise-based intervention was safe (no severe adverse event), feasible (we were able to recruit older BCS and complete the intervention) and acceptable (mean 9.7/10 likelihood of recommending to a friend). In accelerometry data, we observed increased physical activity from baseline to post-intervention at four months, and evidence that activity was more effectively maintained by the exercise group compared to standard care over four research assessments. Future Directions A future randomized efficacy trial will test REJOIN among BCS aged ≥60 within one year of initiating AI therapy. The primary outcome will be joint pain interference during daily activity and the secondary outcome will include AI adherence. As part of this future study, we aim to investigate the biological mechanisms driving AI-related joint pain in older breast cancer survivors, focusing on inflammatory biomarkers such as IL-6, TNFα, and CRP. This will provide evidence to clarify origins of AI-related joint pain and inform future therapeutic strategies. Conclusions: REJOIN offers a scalable approach to reduce AI-associated joint pain and support medication adherence in older BCS. This intervention addresses a critical survivorship gap in older adults and may improve quality of life and treatment outcomes, especially in rural and understudied populations. Citation Format: S. Bluethmann, E. Dressler, M. Caru, H. Klepin, A. Willis, C. Truica, C. Peters, N. Olsen. Using Exercise to Improve Arthralgia and Aromatase Inhibitor Adherence in Older Breast Cancer Survivors: Preliminary Results from a Pilot Randomized Controlled Trial [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 PS1-05-23.