"Prognostic significance of alpha2- and beta2-adrenoceptor gene expression in breast cancer patients".

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, HER2-enriched, basal-like. Epinephrine and norepinephrine, released during chronic 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 tumors also expressed hormone receptors and presented diminished tumor size, grade and not compromised lymph nodes. ADRB2 high expression was found in smaller, low grade, estrogen receptor positive tumors. Both were significantly associated with the absence of metastasis. High expression of ADRA2C was positively associated with increased tumor size and metastatic relapse. We observed a significant increase in DMFS of patients with high ADRA2A (HR 0.54, 95% CI 0.45-0.65, p<0.001) and ADRB2 (0.77, 0.64-0.93, p=0.006) expression and a decrease with ADRA2C high expression (1.45, 1.16-1.81, p=0.001). For patients with luminal tumors, 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 tumors.

CONCLUSIONS: We provide herein new insight for a potential role of ADRA2A and ADRA2C in breast cancer. In low and medium-income countries, their incorporation to routine IHC analysis of biopsies or tumor samples, could provide additional low-cost prognostic factors.