-Original-

Association of Programmed Death-Ligand 1 Expression in Relation to Tumor-Infiltrating Lymphocyte Concentration and Histological Type with Outcomes of Triple-Negative Breast Cancer

Hiroko Yukawa, Akira Hirano, Yuko Ishibashi, Saki Fujita, Asaka Kodera, Yumi Anzai and Masafumi Kurosumi

Department of Breast Surgery, Tokyo Women's Medical University Adachi Medical Center, Tokyo, Japan

Background: Triple-negative breast cancer (TNBC) comprises subgroups with distinct characteristics and histological types. Tumor-infiltrating lymphocyte (TIL) concentration and programmed death-ligand 1 (PD-L1) expression are prognostic factors for TNBC. We analyzed the association of immune cell PD-L1 expression, in relation to histological type and TIL concentration, with TNBC outcomes.
Methods: Data from 86 patients with TNBC treated between 2008 and 2014 were analyzed. Those treated with immune-checkpoint inhibitors (ICIs) were excluded. PD-L1 expression in immune cells was assessed by immunohistochemistry using an SP142 clone. TIL concentration was measured with hematoxylin and eosin staining. Tumor histology was classified as basal type (G1), apocrine type (G2), metaplastic change (G3), special type (G4), and adenoid cystic carcinoma (G5).
Results: The rate of PD-L1 positivity was 2.5%, 17.3%, and 58.6% for patients with TIL concentrations classified as low (TIL-L), moderate (TIL-M), and high (TIL-H) (p < 0.0001). Five-year overall survival (OS) was 78.8% among patients with PD-L1-positive tumors and 81.8% among those with PD-L1-negative tumors. Among TIL-L patients, 5-year OS in PD-L1-positive and -negative tumors was 100% and 77.4%, respectively (p = 0.9993). Among TIL-H patients, 5-year OS for PD-L1-positive and -negative tumors was 73.0% and 83.3%, respectively (p = 0.8241). In multivariate analysis, tumor size and lymphatic vessel invasion were independent prognostic factors for OS.
Conclusions: The rate of PD-L1 positivity was higher in TIL-H patients. Patients classified as TIL-H and PD-L1-positive had worse TNBC outcomes.

J Nippon Med Sch 2025; 92: 331-336

Keywords
TILs, immune checkpoints, PD-L1, triple-negative breast cancer, histological subtypes

Correspondence to
Hiroko Yukawa, Department of Breast Surgery, Tokyo Women's Medical University Adachi Medical Center, 4-33-1 Kohoku, Adachi-ku, Tokyo 123-8558, Japan
yukawa.hiroko@twmu.ac.jp

Received, December 3, 2024
Accepted, March 26, 2025