Purpose: Antitumor immunity plays an important role in the progression of breast cancer. β2-adrenergic receptor (β2AR) was found to regulate the antitumor immune response and breast cancer progression in preclinical studies. To understand the clinical role of β2AR in cancer progression, we investigated the clinicopathological and prognostic significance of β2AR expression in invasive breast cancer.
Methods: β2AR 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 β2AR 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-β2AR expression groups.
Results: Although β2AR was not related to clinicopathological factors across the whole cohort, high β2AR was significantly related to PD-L1 negativity in estrogen receptor (ER)-negative patients. Tumors with high β2AR tended to have low TIL grade, and high β2AR was an independent prognostic factor for reduced survival in ER-negative patients.
Conclusions: β2AR is an independent poor prognostic factor in ER-negative breast cancer. The findings suggest that tumor β2AR regulates immune checkpoint activity, which may have therapeutic implications for patients with ER-negative breast cancer.
Keywords: ER-negative; Immune checkpoint; Invasive breast cancer; PD-L1; Tumor-infiltrating lymphocytes; β2-Adrenergic receptor.