In a cell culture model of highly metastatic, triple-negative breast cancer, the stress hormone adrenaline acted on breast cancer cells via the cell surface beta2-adrenoceptor to promote disease growth and invasion. Because beta-blockers were found to decrease breast cancer cell growth, these results further suggest that beta-blockers might be helpful as adjuvant therapy for patients with aggressive breast cancer. 1

Triple-negative breast cancers do not express human epidermal growth factor receptor 2 (HER2), estrogen receptor, or progesterone receptor. As most breast cancer therapies target 1 of these 3 receptors, triple-negative breast cancers typically require combination therapies and more aggressive treatment. Triple-negative breast cancer accounts for approximately 20% of all breast cancers.

This research found that breast cancer growth and invasion was driven by a positive cAMP-calcium feed-forward loop. The loop was activated by beta2-adrenoceptor. Therefore, administering adrenaline to the breast cancer cells activated the beta2-adrenoceptor, resulting in cells that were progrowth and invasive.

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“Activation of the sympathetic nervous system by stress increases breast cancer metastasis in vivo,” the researchers reported.

Researchers applied adrenaline, a hormone produced during stressful situations, or beta-blocker medication, to aggressive, triple-negative breast cancer cells (the MDA-MB-231HM cell line). Adrenaline administration promoted growth via a cAMP-calcium feed-forward loop. Beta-blocker administration, on the other hand, decreased invasion of the cells. In this model, invasion is indicative of growth and metastasis.

“Previous studies have linked increased stress with accelerated onset of metastasis in some forms of breast cancer,” said Michelle L. Halls, PhD, of the Monash Institute of Pharmaceutical Sciences at Monash University in Parkville, Victoria, Australia, and study leader.

“By understanding how stress accelerates invasion in aggressive breast tumor cells, this work will inform future studies into whether beta-blockers could be a useful adjuvant therapy in the treatment of some aggressive breast cancers.”


1. Pon CK, Lane JR, Sloan EK, Halls ML. The beta2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion. FASEB J. doi:10.1096/fj.15-277798.