Adrenergic receptors in breast cancer

Breast cancer is the most diagnosed malignancy in women worldwide and in the majority of the countries. Breast cancers are classified on the expression of estrogen and progesterone receptor expression and overexpression of human epidermal growth factor receptor 2 (HER2) as luminal, HER2+ and triple negative breast cancer. The intrinsic molecular subtypes match this classification. Cancer diagnosis and treatment cause distress. In both acute and chronic stress, the secreted catecholamines adrenaline and noradrenaline trigger the "fight-or-flight" response. This chapter focuses on the actions of the β2 and α2 adrenergic receptors in several models of breast cancer. The actions of these receptors depend on the model used to investigate them. The β₂-adrenergic receptors seem to exert a dual action. They can directly act on the epithelial cells inhibiting cell proliferation and migration/invasion and indirectly upon the immune microenvironment. The proportion of β2 receptors in each compartment could, therefore, lean the scale to an inhibition or to an exacerbation of tumor growth, invasion and metastasis. All the work points to a beneficial or neutral action of β-blockers on breast cancer. With respect to α2-adrenergic receptors, the investigation performed by our group suggest that the α2B and the α2C receptors are linked to enhanced cell proliferation and tumor growth acting through both the epithelial and the stromal (fibroblastic) compartments while α2A could be beneficial for patients. Some adrenergic compounds could be repurposed for breast cancer treatment due to their very low side effects and very well-known pharmacology.