The animal study provided a model that not only demonstrated that stress can speed up cancer progression, but also detailed the pathway used to change the biology of immune cells that inadvertently promote the spread of cancer to distant organs, where it is much harder to treat.
In addition to documenting the effects of stress on the spread of cancer, the researchers also were able to block those effects by treating stressed mice with beta blockers, which halted the nervous system's reprogramming of the metastasis-promoting immune cells, called macrophages. The findings from the animal model experiments formed the basis of Ganz's efforts to find a breast cancer patient sample in which to test whether exposure to beta blockers could reduce the risk of breast cancer recurrence.
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Working with investigators at Kaiser Permanente Northern California, Ganz examined the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence in a large cohort of early stage breast cancer patients followed for an average of eight years, and for whom pharmacy data on the use of various medications was available. Information about cancer stage, treatments and other chronic conditions also was available.
Of the 1,779 women in the LACE study, 292 experienced a breast cancer recurrence. Ganz said 23 percent of the women in the study were exposed to either a beta blocker or an ACE inhibitor. The women taking these drugs were generally older, post-menopausal and had other health issues, such as being overweight and having hypertension or diabetes.
In analyses that controlled for these differences in health issues, Ganz found that women exposed to ACE inhibitors had a significantly increased risk for recurrence, while those on beta blockers alone had a lower risk of recurrence. Exposure to both beta blockers and ACE inhibitors had an intermediate risk for recurrence, suggesting that the beta blockers might modify the increased risk associated with ACE inhibitor therapy.
"The ACE inhibitor findings were not expected. These observations need to be confirmed and suggest that greater attention should be focused on the potential effect of these commonly used medications on recurrence and breast cancer survival," Ganz said.
In addition, along with Jonsson Cancer Center researchers Steve Cole and Erica Sloan, Ganz is examining the effects of ACE inhibitors in the mouse model system to develop a better understanding of what is happening at the tissue level.
