The association of PD-L1 expression and CD8-positive T cell infiltration rate with the pathological complete response after neoadjuvant treatment in HER2-positive breast cancer

Breast Cancer Res Treat. 2024 May;205(1):17-27. doi: 10.1007/s10549-023-07242-1. Epub 2024 Jan 25.

Abstract

Purpose: Achieving a pathological complete response (pCR) after neoadjuvant therapy in HER2-positive breast cancer patients is the most significant prognostic indicator, suggesting a low risk of recurrence and a survival advantage. This study aims to investigate clinicopathological parameters that can predict the response to neoadjuvant treatment in HER2 + breast cancers and to explore the roles of tumour-infiltrating lymphocytes (TILs), CD8 + T lymphocytes and PD-L1 expression.

Methods: This single-centre retrospective study was conducted with 85 HER2-positive breast cancer patients who underwent surgery after receiving neoadjuvant therapy between January 2017 and January 2020. Paraffin blocks from these patients were selected for immunohistochemical studies.

Results: A complete pathological response to neoadjuvant treatment was determined in 39 (45.9%) patients. High Ki-67 index (> 30%), moderate to high TIL infiltration, PD-L1 positivity and high CD8 cell count (≥ 25) were significantly associated with pCR in univariate analyses (p: 0.023, 0.025, 0.017 and 0.003, respectively). Multivariate regression analysis identified high Ki-67 index (> 30%) and CD8 cell infiltration as independent predictors for pCR in HER2-positive breast cancer.

Conclusions: High Ki-67 index, and high CD8 cell count are strong predictors for pCR in HER2-positive breast cancer. Tumours with high Ki-67 index, high TILs and CD8 infiltration may represent a subgroup where standard therapies are adequate. Conversely, those with low TILs and CD8 infiltration may identify a subgroup where use of novel strategies, including those that increase CD8 infiltration could be applied.

Keywords: CD8; HER2 + breast cancer; Neoadjuvant therapy; PD-L1; Response.

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen* / metabolism
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Prognosis
  • Receptor, ErbB-2* / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • Receptor, ErbB-2
  • CD274 protein, human
  • ERBB2 protein, human
  • Biomarkers, Tumor