Prognostic Significance of Tumor-Infiltrating Lymphocytes and the Tertiary Lymphoid Structures in HER2-Positive Breast Cancer Treated With Adjuvant Trastuzumab

Objectives: Tumor-infiltrating lymphocytes (TILs) have prognostic significance in breast cancer. The tertiary lymphoid structure (TLS) is related to the influx of TILs, and expression of major histocompatibility complex (MHC) I in tumor cells is necessary for the effective action of TILs. Methods: We retrospectively evaluated the relationship of TILs and TLS and the expression of MHC I in 447 HER2-positive breast cancers treated with chemotherapy and 1 year of trastuzumab. Results: TILs were more abundant in hormone receptor (HR)-/HER2+ tumors than in HR+/HER2+ tumors. HR-/HER2+ breast cancers with abundant TILs showed a higher histologic grade, the absence of lymphovascular invasion, the presence of peritumoral lymphocytic infiltration, moderate to abundant TLSs in adjacent tissue, and stronger HLA-ABC and HLA-A expression. Abundant TILs and the absence of lymphovascular invasion were found to be good, independent prognostic factors for disease-free survival in patients with HR-/HER2+ breast cancer. The level of TILs was not associated with the patients' prognosis in HR+ tumors. Conclusions: Abundant TILs are an independent prognostic factor in HR-/HER2+ breast cancers. Evaluation of TILs in HR-/HER2+ breast cancers may provide valuable information regarding the prognosis of patients treated using adjuvant chemotherapy and trastuzumab.