Breast cancer is the most frequent malignancy in women. Several reports demonstrated that adrenergic receptors (ARs) are involved in breast cancer. Here we observed that epinephrine (Epi), an endogenous AR agonist, caused opposite effects in non-tumorigenic (MCF-10A and HBL-100) and tumor cells (MCF-7 and MDA-MB-231). Thus, Epi, in non-tumor breast cells, as well as isoproterenol (β-agonist), in all cell lines, maintained a benign phenotype, decreasing cell proliferation and migration, and stimulating cell adhesion. β-AR expression and cAMP levels were higher in MCF-10A than in MCF-7 cells. β2-AR knock-down caused a significant increase of cell proliferation and migration, and a decrease of cell adhesion both in basal and in Iso-stimulated conditions. Coincidently, β2-AR over-expression induced a significant decrease of cell proliferation and migration, and an increase of cell adhesion. Therefore, β2-AR is implied in cell phenotype and its agonists or antagonists could eventually complement cancer therapy.

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Aims Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. It was classified within molecular intrinsic subtypes: luminal A, luminal B, human epidermal growth factor receptor 2‐enriched and basal‐like. Epinephrine and norepinephrine, released during stress, bind to adrenoceptors. α2‐adrenoceptors are encoded by the ADRA2A, ADRA2B and ADRA2C genes and β2 by ADRB2. Methods We compiled several publicly available Affymetrix gene expression datasets, obtaining a large cohort of 1924 patients with distant metastasis‐free survival (DMFS) data and evaluated the association between adrenoceptor expression, clinicopathological markers and outcome. Results ADRA2A high expressing tumours also expressed hormone receptors and presented diminished tumour size, grade and not compromised lymph nodes. ADRB2 high expression was found in smaller, low grade, oestrogen receptor‐positive tumours. Both were significantly associated with the absence of metastasis. High expression of ADRA2C was positively associated with increased tumour size and metastatic relapse. We observed a significant increase in DMFS of patients with high ADRA2A (hazard ratio 0.54, 95% CI 0.45–0.65, P < .001) and ADRB2 (0.77, 0.64–0.93, P = .006) expression and a decrease with ADRA2C high expression (1.45, 1.16–1.81, P = .001). For patients with luminal tumours, ADRA2A was the only factor that retained its significance as an independent predictor of DMFS while ADRA2C expression was an independent predictor for worse prognosis in basal‐like tumours. Conclusions We herein provide new insight for a potential role of ADRA2A and ADRA2C in breast cancer. In low‐ and medium‐income countries, their incorporation to routine immunohistochemistry analysis of biopsies or tumour samples, could provide additional low‐cost prognostic factors.