Abstract P6-21-05: Concurrent exercise and chemotherapy in preclinical breast cancer models

Abstract

Abstract The benefits of exercise following a cancer diagnosis is increasingly recognized. Increased physical activity is associated with reduced breast cancer recurrence and breast cancer specific mortality. However, the mechanisms underpinning this effect are still under investigation. The role of exercise as an adjunct to systemic therapy for breast cancer remains unclear. We hypothesize that exercise may exert an anti-tumor effect and a change in tumor immune cell infiltration. Methods We evaluated the effect of exercise alone and in combination with chemotherapy in preclinical patient-derived TNBC xenografts (PDX) established in Nude mice and PyMT mouse tumor models. Mice were individually housed in boxes equipped with running wheels and randomized to 1) clamped wheels (sedentary controls), 2) doxorubicin (Dox, 2mg/kg/week), 3) exercise (Ex) and 4) Ex + Dox. Daily distance run was measured. One week after randomization (acclimatization period), the intervention was commenced. Body composition was measured at randomization and at end point. Tumors were harvested after 5 weeks of intervention or at ethical endpoint. Tumor immune infiltrates were analyzed, and transcriptomic analysis performed. Results In the TNBC PDX model, there was no difference in tumor volume at randomization (p=0.96), or cumulative distance run after 1 week of acclimatization to the running wheel (p=0.47). At 5 weeks, Ex alone significantly reduced tumor growth rate compared with controls (relative reduction 10%, p=0.025). There was no difference between the other interventions. Mice randomized to Ex + Dox ran a shorter cumulative distance over 5 weeks compared with Ex alone (103.6 ± 16.2km vs 168.8 ±23km, p=0.028). There was no correlation between distance run and tumor volume in either of the treatment cohorts involving exercise (p=0.39). PyMT, transcriptomic and immune cell infiltration analysis will be reported. At baseline, there was no significant difference in mean total body mass (TBM), lean mass (LM) or fat mass (FM) between the intervention groups (p>0.05). At 5 weeks, the mean TBM and LM in both groups treated with Dox was significantly lower than Ex only and controls. The Ex and the control mice gained weight (11%), compared with Dox only and Ex + Dox mice which did not gain weight (0% and -6% respectively). Therefore exercise had no significant impact on TBM or LM at 5 weeks, but Dox resulted in loss of TBM and LM compared with mice not treated with Dox. Conclusion Exercise significantly reduced tumor growth compared with sedentary controls in our preclinical TNBC PDX model, however there was not synergistic effect seen with Dox. Cumulative doses of Dox resulted in weight loss and loss of lean mass, and reduced the cumulative running distance, compared with mice not treated with Dox. Citation Format: Wahlroos S, Wilkinson A, Gallego-Ortega D, Febbraio M, Lim E. Concurrent exercise and chemotherapy in preclinical breast cancer models [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-05.