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. 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 (Ex) +/- doxorubicin (Dox) in a preclinical TNBC PDX model and a PyMT mouse tumor model after 5 weeks of intervention. Individually housed mice in boxes equipped with running wheels were randomized to 1) locked wheels (controls), 2) Dox (2mg/kg/week), 3) Ex and 4) Ex + Dox. Apoptosis and cell proliferation, as well as immune cell infiltration was done with IHC.
Results
In the TNBC PDX model, 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 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 (p=0.39). There was no difference in cell proliferation between the arms, but a trend towards increased apoptosis in the Ex only arm. A significant increase in stromal NK cells was seen in the Ex only arm, compared to the two Dox arms (<0.05).
In the PyMT model, there was no effect of exercise on tumour volume. There was a trend towards increased NK cell in the tumour stroma in the Ex arms, and the same trend was observed in the CD4 and CD8 immune cell population.
Conclusion
Exercise significantly reduced tumor growth compared with sedentary controls in our preclinical TNBC PDX model only, however there was not synergistic effect seen with Dox. Ex appears to increase intratumoural stromal immune cell infiltration.