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

• Published in: Breast cancer research and treatment 2019-10, Vol.177 (3), p.603-610
• Main Authors: Kurozumi, Sasagu, Kaira, Kyoichi, Matsumoto, Hiroshi, Hirakata, Tomoko, Yokobori, Takehiko, Inoue, Kenichi, Horiguchi, Jun, Katayama, Ayaka, Koshi, Hiromi, Shimizu, Akira, Oyama, Tetsunari, Sloan, Erica K., Kurosumi, Masafumi, Fujii, Takaaki, Shirabe, Ken
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Antitumor activity; Biomarkers; Breast cancer; Cancer research; Estrogen receptors; Immune checkpoint; Immune response; Immunohistochemistry; Invasiveness; Lymphocytes; Medical prognosis; Medicine; Medicine & Public Health; Oncology; Patients; PD-L1 protein; Preclinical Study; Tumor-infiltrating lymphocytes; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-019-05341-6

Purpose Antitumor immunity plays an important role in the progression of breast cancer. β 2 -adrenergic receptor (β 2 AR) was found to regulate the antitumor immune response and breast cancer progression in preclinical studies. To understand the clinical role of β 2 AR in cancer progression, we investigated the clinicopathological and prognostic significance of β 2 AR expression in invasive breast cancer. Methods β 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 β 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-β 2 AR expression groups. Results Although β 2 AR was not related to clinicopathological factors across the whole cohort, high β 2 AR was significantly related to PD-L1 negativity in estrogen receptor (ER)-negative patients. Tumors with high β 2 AR tended to have low TIL grade, and high β 2 AR was an independent prognostic factor for reduced survival in ER-negative patients. Conclusions β 2 AR is an independent poor prognostic factor in ER-negative breast cancer. The findings suggest that tumor β 2 AR regulates immune checkpoint activity, which may have therapeutic implications for patients with ER-negative breast cancer.