Prognostic Value of Tertiary Lymphoid Structures in Primary Breast Cancer and Their Association With Immune Microenvironment

ABSTRACT This study aimed to investigate the distribution, maturity, and prognostic significance of tertiary lymphoid structures (TLS) in primary breast cancer (BC), and to analyze the relationship between TLS clinicopathological features and the tumor immune microenvironment. Sixty postoperative tumor samples from patients with primary BC were retrospectively analyzed. The presence and maturity of TLS in tumor tissues were evaluated by immunohistochemical staining. The association of status and clinicopathological characteristics of TLS with immune cell infiltration was analyzed. Recurrence‐free survival (RFS) and predictive factors were assessed using Kaplan–Meier survival analysis and univariate/multivariate logistic regression. TLS was detected in 35 (58.33%) patients, including 23 cases of secondary follicle‐like TLS, 8 cases of early TLS, and 4 cases of primary follicle‐like TLS. Compared with the non‐TLS group, the TLS group showed significantly higher expression of estrogen receptor and progesterone receptor ( p < 0.05). The presence of TLS was significantly associated with improved RFS (HR = 0.163, p = 0.035), with secondary follicle‐like TLS showing the most favorable survival trend. TLS‐positive tumors had significantly increased infiltration of CD4 + T cells ( p = 0.004), while CD8 + T cell infiltration was slightly higher but not statistically significant. The presence of TLS, especially mature TLS, is associated with favorable clinicopathological features and improved prognosis in patients with primary BC, along with increased CD4 + T cell infiltration, suggesting an important role of TLS in regulating the tumor immune microenvironment. TLS may serve as a potential biomarker for prognosis evaluation and a target for immunomodulatory strategies in BC.