The beta-2 adrenergic receptor (ADRB2) drives tumor proliferation and induces treatment resistance in preclinical models of HER2+ breast cancer. This study aimed to evaluate the predictive and prognostic role of ADRB2 expression as a biomarker in HER2+ breast cancer patients.
ADRB2 expression was retrieved from 2 datasets comprising gene expression data of HER2+ early breast cancer patients: 1 dataset included patients who did not receive systemic treatment to assess disease-free survival (DFS; N = 175) and 1 dataset included patients who received neoadjuvant treatment to assess pathologic complete response (pCR; N = 207). Survival was estimated with the Kaplan Meier method and the Cox regression model was used for uni-multivariate analyses. The correlation of ADRB2 expression with gene signatures related to proliferation, invasiveness, immune activation and angiogenesis was performed.
High ADRB2 expression was associated with improved DFS (HR 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.0068), with a more pronounced impact in HER2+/ER+ patients (HR 0.45, 95%CI 0.24-0.84, p = 0.0097). No association between ADRB2 expression and pCR was observed (OR 1.14, 95%CI 0.63–2.10, p = 0.67). ADRB2 expression was associated with a low expression of angiogenesis-related genes (VEGF -0.21, p = 0.006) and a high expression of genes related to immune activation (Perez +0.41, p < 0.001; STAT1 +0.30, p = 0.014; IRM +0.28, p = 0.017).
Opposing our hypothesis, ADRB2 high expression was a positive prognostic factor in HER2+ early breast cancer. The low expression of angiogenesis-related and the high expression of immune-related genes associated with ADRB2 expression may justify our findings.
Institut Jules Bordet.
Has not received any funding.
R.C. Bitton: Speaker-honoraria: Boehringer Ingelheim, Janssen; Travel grants: AstraZeneca. C. Sotiriou: Patents on gene expression and methylation signatures; Advisory boards, speaker, travel support for medical meetings: Amgen, Astellas, AstraZeneca, Bayer, Celgene, NanoString Technologies, Novartis, Pfizer, Roche. E. de Azambuja: Honoraria, research grant (to the institution): Roche-Genentech; Travel grants outside the submitted work: Roche-Genentech, GlaxoSmithKline. All other authors have declared no conflicts of interest.