Effects of Exercise Intensity and Time on Efficacy of Paclitaxel and Doxorubicin and Immune Microenvironment in the 4T1 Breast Cancer Model.

Background: Chemotherapy is the mainstay treatment for metastatic triple negative breast cancer (TNBC). However, many patients still die of metastasis after chemotherapy, making it worthwhile to develop strategies to increase chemotherapy efficacy when treating metastatic TNBC. Previous studies have shown that exercise has the potential to inhibit breast cancer metastasis and enhance the effect of chemotherapy, and the level of exercise had a significant effect on tumor metastasis. However, the effect of different doses of exercise-referring to the combination of intensity and duration-on tumor metastasis during breast cancer chemotherapy remains unclear. Methods: 4T1 TNBC subcutaneous tumors were treated with paclitaxel (PTX) and doxorubicin hydrochloride (DOX), as well as different intensities and duration of exercise. Tumor growth, survival, metastatic burden, and the frequencies of some important immune cells were measured to determine the effects, and underlying mechanism, of different exercise doses on the anti-cancer efficacy of PTX and DOX. Results: The combination of high-dose exercise with PTX and DOX promoted metastasis formation, shortened mouse survival, and up-regulated the neutrophil/T lymphocyte ratio in the lungs. In contrast, low-dose exercise synergized with PTX and DOX to suppress metastasis, prolonged the survival of mice, decreased the neutrophil/T lymphocyte ratio, and up-regulated the percentages of NK cells within the metastatic microenvironment. The combination of different exercise dose with PTX and DOX did not affect primary tumor growth. Conclusions: The intensity and time of exercise might affect efficacy of PTX and DOX; however, TNBC patients should be careful concerning the intensity and time of exercises while undergoing chemotherapy. Breast cancer patients might be best served by participating in low levels of exercise, and avoiding excessive exercise, during PTX and DOX therapy.