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

Am J Clin Pathol. 2015 Aug;144(2):278-88. doi: 10.1309/AJCPIXUYDVZ0RZ3G.


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.

Keywords: Breast carcinoma; HER2; Lymphocytes; MHC I; Tertiary lymphoid structure; Trastuzumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Histocompatibility Antigens Class I
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Lymphoid Tissue / pathology*
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Tissue Array Analysis
  • Trastuzumab


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Histocompatibility Antigens Class I
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab