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

RIVERO E; MARTINEZ L; BRUQUE C; GARGIULO L; BRUZZONE A; LUTHY IA

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2019

0306-5251

Breast cancer is the most frequently diagnosed and the leading cause of death by cancer 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 adrenergic receptors, divided into nine subtypes. α2-receptors are encoded by the ADRA2A, ADRA2B and ADRA2C genes and β2 by the ADRB2 gene. 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 associations between their expression, clinicopathological markers and outcome. ADRA2A high expressing tumors express hormone receptors and negatively correlated with increased tumor size, grade and compromised lymph nodes. ADRB2 high expression was found in smaller, low grade, estrogen receptor positive tumors. Both receptors were significantly associated with absence of metastatic recurrence. Contrarily, high expression of ADRA2C was positively associated with increased tumor size and metastatic relapse. We observed a significant increase in DMFS of patients with ADRA2A and ADRB2 high expression tumors and a decrease in ADRA2C high expression tumors. For patients with luminal A 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.We provide herein new insight for a potential role of ADRA2A and ADRA2C in breast cancer. In low and medium-income countries, these receptors could be easily incorporated to routine IHC analysis of biopsies or tumor samples, providing additional low-cost prognostic factors.