title: Prognostic Significance of Tumor-Infiltrating Lymphocytes and the Tertiary Lymphoid Structures in HER2-Positive Breast Cancer Treated With Adjuvant Trastuzumab.
abstract: OBJECTIVE
  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.
authors.affiliation: From the Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea;
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea; and.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: From the Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea;
authors.forename: In Ah
authors.initials: IA
authors.lastname: Park
authors.affiliation: From the Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea;
authors.forename: In Hye
authors.initials: IH
authors.lastname: Song
authors.affiliation: Departments of Surgery and.
authors.forename: Jong Han
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: From the Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; gygong@amc.seoul.kr.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008221:Lymphoid Tissue / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D046888:Tissue Array Analysis; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast carcinoma; HER2; Lymphocytes; MHC I; Tertiary lymphoid structure; Trastuzumab