Zhou Danyang, Li Mei, Yasin Mohamed Hussein, Lu Qianyi, Fu Jia, Jiang Kuikui, Hong Ruoxi, Wang Shusen, Xu Fei
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, China.
NPJ Breast Cancer. 2023 Apr 21;9(1):30. doi: 10.1038/s41523-023-00527-0.
This study aimed to investigate the prognostic value of AR in HER2+ nonmetastatic breast invasive ductal carcinoma (IDC) and its relationship with the immune microenvironment. HER2+ nonmetastatic breast IDC patients diagnosed by pathology who underwent surgery at Sun Yat-sen University Cancer Center from 2016 to 2017 were included. AR+ and AR- breast IDC samples were matched 1:1 in age, T stage, and N stage for immune infiltration analysis. A total of 554 patients with HER2+ nonmetastatic breast cancer were included in this retrospective study, regardless of HR status. The cut-off value for AR was set at 10%. ER+ (p < 0.001) and PR+ (p < 0.001) were associated with positive AR expression. Kaplan-Meier survival curve analysis suggested that AR was closely correlated with overall survival (OS) (p = 0.001) but not disease-free survival (DFS) (p = 0.051). After eliminating the potential impact caused by HR, AR also predicted longer OS (p = 0.014) and was an independent predictive factor for OS of HER2+HR- nonmetastatic breast IDC patients, as revealed by multivariate analysis (p = 0.036). For AR+ and AR- matched HER2+HR- patients, TILs (p = 0.043) and PD-L1 (p = 0.027) levels were significantly lower in AR+ patients. The strongest negative correlation was observed between AR and PD-L1 (Pearson's r = -0.299, p = 0.001). AR+ status was markedly related to better OS in HER2+HR- nonmetastatic breast cancer patients, while a negative correlation was observed between AR and PD-L1/TILs. We provide new insights into the prognostic value of AR and its association with the immune microenvironment to optimize treatment strategies in HER2+ nonmetastatic breast IDCs.
本研究旨在探讨雄激素受体（AR）在人表皮生长因子受体2（HER2）阳性非转移性乳腺浸润性导管癌（IDC）中的预后价值及其与免疫微环境的关系。纳入2016年至2017年在中山大学肿瘤防治中心接受手术治疗、经病理诊断为HER2阳性非转移性乳腺IDC的患者。对AR阳性和AR阴性乳腺IDC样本按年龄、T分期和N分期1:1匹配，进行免疫浸润分析。本项回顾性研究共纳入554例HER2阳性非转移性乳腺癌患者，不考虑激素受体（HR）状态。AR的截断值设定为10%。雌激素受体（ER）阳性（p < 0.001）和孕激素受体（PR）阳性（p < 0.001）与AR阳性表达相关。Kaplan-Meier生存曲线分析表明，AR与总生存期（OS）密切相关（p = 0.001），但与无病生存期（DFS）无关（p = 0.051）。排除HR造成的潜在影响后，AR仍可预测更长的OS（p = 0.014），多因素分析显示，AR是HER2阳性HR阴性非转移性乳腺IDC患者OS的独立预测因素（p = 0.036）。对于AR阳性和AR阴性匹配的HER2阳性HR阴性患者，AR阳性患者的肿瘤浸润淋巴细胞（TILs）水平（p = 0.043）和程序性死亡受体配体1（PD-L1）水平（p = 0.027）显著较低。AR与PD-L1之间观察到最强的负相关性（Pearson相关系数r = -0.299，p = 0.001）。在HER2阳性HR阴性非转移性乳腺癌患者中，AR阳性状态与更好的OS显著相关，而AR与PD-L1/TILs之间呈负相关。我们为AR的预后价值及其与免疫微环境的关联提供了新的见解，以优化HER2阳性非转移性乳腺IDC的治疗策略。
