Tertiary lymphoid structures: Prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer

Background Tumour-infiltrating lymphocytes (TILs) have a strong prognostic significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs). Objective To carry out a histological analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs and their prognostic significance in TNBC. Methods We retrospectively analysed 769 patients with TNBC. Results TILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumour stroma, high levels of peritumoral lymphocytic infiltration and moderate to abundant TLSs in adjacent tissue. TILs, the degree of peritumoral lymphocytic infiltration and adjacent TLSs were prognostic factors for disease-free and overall survival. Although the TIL level did not have a prognostic value in stage I, it added significant prognostic information for stages II and III. Conversely, patients with high levels of TILs did not show prognostic differences according to the pTNM stage. Patients with high levels of TILs (>60%) and moderate to abundant TLSs had significantly better disease-free survival than those with high levels of TILs but none or few TLSs. Conclusions TLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.