An NCI-designated Comprehensive Cancer Center
By Denise Heady | April 25, 2016

Breakthroughs - Beta Blockers could slow or stop cancer growth From L-R: Michael Lew, M.D., John Raytis, M.D., Cecilia Choy, Ph.D., and Rahul Jandial, M.D., Ph.D.

A little stress can be beneficial for the brain and body. It can make us more resilient and help motivate us to be more productive. But chronic stress has long been linked to increasing cancer risk, and recent studies show that stress hormones play a direct role in supporting cancer growth.

Breast cancer patients in particular are at greater risk of the disease spreading to the brain, so the dangers of stress are amplified.

But in a hopeful development, researchers at City of Hope have found that beta-blockers, a common medication used to treat high blood pressure, may be one answer to stopping cancer growth from stress — particularly brain metastases caused from breast cancer. Signs point to the medication being especially effective in deterring breast cancer recurrence and metastasization when used during the crucial high-stress window surrounding surgery.

The researchers’ findings were recently published online in Oncology Reports.

“Stress, which leads to adrenaline release, has been suspected to fuel cancer growth,” said study co-author Cecilia Choy, Ph.D., a graduate student in the Jandial laboratory, “and this research shows that by blocking adrenaline receptors in breast cancers, they are less successful in spreading to and growing in the brain.”

Cancer cells are under the relentless drive to spread, and this metastasis is responsible for a majority of cancer-related deaths. The most ominous part of the body to which cancer can spread is the brain, leading to what is called brain metastasis.

Brain metastases are increasingly the first site of recurrence for women with breast cancer, particularly Her2 positive subtypes. Since this is a relatively new clinical phenomenon that arose after significant gains in controlling systemic disease with molecular therapies, the biology of brain metastases is poorly understood.

The brain is highly unique in its anatomy and biology, so breast cancer cells circulating in the blood would need to exhibit unique features to exploit the brain’s native nutrient sources, such as neurochemicals. Interestingly, adrenaline is a major neurochemical abundant during stress. It narrows blood vessels and results in elevated blood pressure.

Neurosurgeon and scientist Rahul Jandial, M.D., Ph.D., associate professor in the Division of Neurosurgery, together with Michael Lew, M.D., clinical professor and chair of the Department of Anesthesiology, and John Raytis, M.D., assistant clinical professor in the Department of Anesthesiology, investigated the underlying cancer biology of brain metastasis to find out if they could somehow modulate the stress response to decrease the rate of cancer spread in breast cancer patients.

“Because biological systems, both healthy and cancerous, strive for efficiency,” said Jandial, “we wondered if breast cancer cells evolved to respond to natural brain chemicals such as epinephrine.”

The project stemmed from earlier work done by Lew and Raytis, who had looked at patient data using City of Hope bioinformatics to see if patients who were on medications with the ability to block the surgical stress response had lower cancer recurrence and metastases after surgery.

“We looked back at 10 years of patient data and saw some interesting trends,” said Raytis, one of the lead authors of the earlier study. “We saw that for Stage 2 breast cancer patients who were on a beta-blocker at or near the time of their surgery, their reoccurrence rate was lower. This trend got us interested in pursuing the mechanism by which beta-blockers might be able to reduce postoperative cancer recurrence and metastases. We reached out to Dr. Jandial and formed an interdepartmental collaboration to further examine our findings.”

While it is still too early to recommend blood pressure medication for breast cancer patients, this type of drug shows lots of promise and encourages further investigation of potential benefits. “Eventually, we hope that it will be possible to identify breast cancer patients who could benefit from taking beta-blockers either at the time of their surgery or for more extended periods of time,” added Lew.


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