The prognostic value and immune microenvironment association of androgen receptor in HER2 positive early breast invasive ductal carcinoma

Background: The prognosis of HER2+ early breast cancer is heterogeneous. AR, as an indicator of prognosis and treatment, is uncertain in HER2+ subtypes. We aimed to investigate the prognostic value of AR and the relationship between AR expression and immune microenvironment in HER2+ early breast invasive ductal carcinoma (IDC). Methods: HER2+ early breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were the main population. All patients included performed AR test and their clinicopathological data were collected. The disease-free survival (DFS) and overall survival (OS) were evaluated by the Kaplan–Meier method and Cox proportional hazards model. AR+ and AR- breast IDCs were matched 1:1 according to age, T stage and N stage for immune infiltration analysis. Results: A total of 554 patients with HER2+ early breast cancer were included in this retrospective study, regardless of HR status. Taking 10% as the cutoff values of AR, 81.6% of patients were AR positive and 18.4% were AR negative. ER+ (P<0.001) and PR+ (P<0.001) had significant relations with the positive expression of AR. Kaplan-Meier survival curves analysis suggested that AR had close links with OS (P=0.001), not DFS (P=0.051). Eliminating the potential impact caused by HR, AR also predicted a longer OS (P=0.014) and AR was an independent impact factor for OS by multivariate analysis (P=0.036) in HER2+HR- early breast IDC patients. In AR+ and AR- matched HER2+HR- patients, TILs (P=0.043) and PD-L1 (P=0.027) is significantly low in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson’s r =-0.299, P=0.001). AR+ seemed to trend a favorable clinical survival in HER2+HR- IDCs with low TILs or positive PD-L1. Conclusions: AR+ were markedly related to the better OS in HER2+HR- early breast cancer, while the negative correlation was observed between AR and PD-L1/TILs. We provided new insights for the prognostic value and immune microenvironment association of AR to optimize treatment strategies in HER2+ early breast IDCs.