Prognostic Significance of Fibrotic Focus and Tumor Infiltrating Lymphocytes in Breast Cancer According to Molecular Subtypes

Abstract

Purpose: This study aimed to analyze the association between fibrotic focus (FF) and tumor-infiltrating lymphocytes (TILs) and to determine the prognostic significance of FF and TILs in the breast according to its molecular subtypes.Methods: The study included patients who underwent surgical treatment for breast cancer, for whom tissue samples were available. FF within the tumor and TILs in breast cancer tissues were evaluated. Clinicopathological characteristics were reviewed from medical records.Results: FF and TILs were present in 31.3% and 81.7% of the patients, respectively. FF and TILs showed a positive correlation. FF were significantly associated with tumor size, lymphovascular invasion, regional lymph node metastasis, and tumor stage. TILs were significantly associated with menopausal status, histologic grade, tubule formation, nuclear grade, mitosis, human epidermal growth factor receptor 2 (HER2) overexpression, molecular subtype of breast cancer, and the number of cluster of differentiation 8+ T cells. In TIL-positive cases, FF were significantly associated with tumor size, regional lymph node metastasis, extranodal extension, lymphovascular invasion, tumor stage, recurrence-free survival, and overall survival (OS). Based on HER2 overexpression status, TILs were significantly associated with tumor size, tumor necrosis, histologic grade, estrogen receptor status, and epidermal growth factor receptor expression in HER2-negative breast cancer. Further, in HER2-negative breast cancer, OS and recurrence-free survival were significantly associated with FF. The OS of FF-positive patients was significantly shorter than that of FF-negative patients.Conclusion: Our study showed an association between FF and TIL levels in breast cancer, indicating that FF are associated with poor prognostic factors for breast cancer and poor OS, and that TILs are associated with HER2 overexpression. However, further studies are needed to elucidate the interactions between FF and TILs in breast cancer.