Prognostic and predictive impact of beta-2 adrenergic receptor expression in HER2-positive breast cancer

Abstract Background Beta-2 adrenergic receptor (ADRB2) mediates proliferation and treatment resistance in preclinical models of HER2+ breast cancer. We evaluated ADRB2 gene expression as a prognostic and predictive biomarker in HER2+ early breast cancer patients. Methods ADRB2 expression was retrieved from HER2+ patients enrolled in the FinHer study (N=202), and 2 public datasets containing data from HER2+ early breast cancer patients: one including patients who did not receive systemic treatment (disease-free survival [DFS] dataset; N=175) and another including patients who received neoadjuvant treatment (pathologic complete response [pCR] dataset; N=207). Survival was estimated with Kaplan-Meier method and Cox regression was used for uni-multivariate analyses. ADRB2 expression was correlated with several gene signatures. Results ADRB2 high expression was associated with improved DFS rates in HER2+ patients (HR 0.52, 95% confidence interval [CI] 0.32-0.84, p=0.0068). No association between ADRB2 expression and pCR was observed (OR 1.14, 95%CI 0.63-2.10, p=0.67). No association between ADRB2 and relapse-free survival (RFS) was observed in HER2+ patients enrolled in the FinHer study (HR 0.93; 95% CI 0.69-1.25; p=0.61). ADRB2 was associated with a low expression of angiogenesis-related (VEGF -0.38, p Conclusions Opposing our initial hypothesis, a high ADRB2 expression may be a favourable prognostic factor in HER2+ early breast cancer patients. This association appears to be mediated by anti-proliferative, anti-angiogenic and immunogenic effects of ADRB2.