Objective: Fever-range whole body hyperthermia (FR-WBH) helps control tumor growth in vivo. Mediation of this effect is likely through a combination of factors including increased blood flow that could alter important microenvironmental parameters affecting tumor growth such as increased recruitment of immune effector cells to the tumor site. One concern is that this increased blood flow could facilitate increased metastasis. We investigated whether FR-WBH (39.5ºC) affects metastasis using the 4T1 mouse mammary tumor model-an orthotopic model that undergoes spontaneous metastatic spread in a clinically relevant pattern.

Methods: BALB/c mice were inoculated with 1 x 10⁶ 4T1 cells in the mammary fat pad. Control groups were maintained under normothermic conditions, whereas experimental groups were treated with FR-WBH performed at 7, 14, and 21 days post 4T1 inoculation. On days 14, 21 and 28 post 4T1 inoculation, lungs from 6 mice in both groups were recovered, weighed and prepared for histology. The degree of metastasis to the lungs was determined by comparison of lung weight and the presence of metastases in histological preparations.

Results: Results of this experiment show that FR-WBH does not affect the degree of metastasis to the lungs in the 4T1 mouse mammary tumor model. Lungs weights of normothermic and WBH treated mice were compared after 2 weeks (1 WBH), 3 weeks (2 WBH) and 4 weeks (3 WBH) and the weights at these three intervals were not significantly different. We are currently evaluating histological features of heated tumors in comparison to those in control animals.

Conclusions: FR-WBH is currently being used as an adjuvant therapy and it is imperative to determine the effects of FR-WBH on metastasis. Since FR-WBH does increase tumor blood flow then one could speculate that metastasis of shed tumor cells might be increased in a patient undergoing FR-WBH. Based on the results of this experiment using a clinically relevant model of metastatic breast cancer we are encouraged that FR-WBH, in fact, did not increase metastatic disease burden.
Supported by NIH P01 CAP14045 and ROI CA71599