ACE Inhibitors May Increase Risk of Recurrence in Breast Cancer Survivors

ACE inhibitors, commonly used to control high blood pressure and heart failure in women, may be associated with an increased risk of recurrence in women who have had breast cancer, according to a study by researchers at UCLA’s Jonsson Comprehensive Cancer Center.

Beta blockers, used to control high blood pressure and cardiac arrhythmias, appear to have a protective effect, helping to prevent recurrence. When used together, beta blockers appear to help ameliorate the negative affect of ACE inhibitors, said Dr. Patricia Ganz, director of cancer prevention and control research at UCLA’s Jonsson Cancer Center and first author of the study.

Ganz characterized the results of the retrospective analysis done using data from the Life After Cancer Epidemiology (LACE) study, which includes 1,779 Kaiser patients diagnosed with early stage breast cancer, as “hypothesis-generating only.” She underscored that the results need further corroboration in other, larger clinical data bases.

However, the surprising negative effect of the ACE inhibitors on chances for recurrence is, at the least, cause for caution.

“The message from this is we have to be aware of other chronic health problems and medications that patients take after their diagnosis of breast cancer,” said Ganz, an international expert in the fields of quality of life after cancer and cancer survivorship. “We are learning that some medications, while they may be very helpful for treating cardiovascular disease and hypertension, may have an adverse effect on breast cancer survivors.”

In the study, just published online in the journal Breast Cancer Research and Treatment, Ganz speculated that ACE inhibitors and beta blockers may work differently in the breast cancer microenvironment, affecting different pathways of inflammation, and that may be the key to their disparate impact on breast cancer recurrence.

It’s long been thought that inflammation fuels cancer growth in humans. A September 2010 Jonsson Cancer Center study showed that chronic stress acts as a sort of fertilizer that feeds breast cancer progression through inflammatory signaling, significantly accelerating the spread of disease in mouse models.

The researchers discovered that stress was biologically reprogramming the immune cells trying to fight the cancer, transforming them from soldiers protecting the body against disease into aiders and abettors. The study found a 30-fold increase in cancer spread throughout the bodies of stressed mice compared to those that were not stressed.

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.