β2-Adrenergic receptor expression is associated with biomarkers of tumor immunity and predicts poor prognosis in estrogen receptor-negative breast cancer

Purpose Antitumor immunity plays an important role in the progression of breast cancer. beta(2)-adrenergic receptor (beta(2)AR) was found to regulate the antitumor immune response and breast cancer progression in preclinical studies. To understand the clinical role of beta(2)AR in cancer progression, we investigated the clinicopathological and prognostic significance of beta(2)AR expression in invasive breast cancer. Methods beta(2)AR levels in breast tumors were evaluated by immunohistochemistry in a well-characterized patient cohort with long-term follow-up (n = 278). We evaluated the relationship of beta(2)AR expression to patient survival and clinicopathological factors, including immune biomarkers such as tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression. Breast cancer-specific survival was compared between high- and low-beta(2)AR expression groups. Results Although beta(2)AR was not related to clinicopathological factors across the whole cohort, high beta(2)AR was significantly related to PD-L1 negativity in estrogen receptor (ER)-negative patients. Tumors with high beta(2)AR tended to have low TIL grade, and high beta(2)AR was an independent prognostic factor for reduced survival in ER-negative patients. Conclusions beta(2)AR is an independent poor prognostic factor in ER-negative breast cancer. The findings suggest that tumor beta(2)AR regulates immune checkpoint activity, which may have therapeutic implications for patients with ER-negative breast cancer.