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

MARTÍNEZ L; BRUZZONE A; RIVERO E; GARGIULO L; BRUQUE CD; LÜTHY IA

British Journal of Clinical Pharmacology

Oxford : Wiley-Blackwell

Lugar: Londres; Año: 2019 vol. 85 p. 2143 - 2154

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. Alpha2-adrenoceptors are encoded by the ADRA2A, ADRA2B and ADRA2C genes and Beta2 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