PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy

Int J Cancer. 2017 Mar 15;140(6):1384-1395. doi: 10.1002/ijc.30552.

Abstract

This study sought to investigate the prevalence of programmed death ligand 1 (PD-L1) and its prognostic value in patients with residual tumors after neoadjuvant chemotherapy (NCT) for locally advanced breast cancer. A total of 309 patients considered as non-pathological complete responders (non-pCR) after NCT followed by mastectomy were selected. The expression of PD-L1 and tumor-infiltrating lymphocytes (TILs) in residual breast cancer cells was assessed by immunohistochemistry in surgical specimens. The median density was used to classify PD-L1 expression from low to high. The prognostic value of various clinicopathological factors was evaluated. The expression of PD-L1 was more commonly observed in patients with low levels of total TILs (p < 0.001), high levels of FOXP3+ TILs (p < 0.001) and low levels of CD8+ TILs (p < 0.001). This served as an independent prognostic factor for both relapse-free survival (Hazard ratio = 1.824, p = 0.013) and overall survival (OS) (Hazard ratio = 2.585, p = 0.001). High expression of PD-L1 was correlated to worse survival, which is most significantly observed in triple-negative patients. Patients classified as PD-L1-high/CD8-low exhibited relatively unfavorable survival, whereas patients with either low expression of PD-L1 or high expression of CD8 had similar outcomes. PD-L1 expression in residual tumor can be used as a prognostic marker in non-pCR patients after receiving NCT for breast cancer, which highlights the importance of immune evasion in the therapeutic vulnerability of chemoresistant cancer cells as well as the potential of anti-PD-L1 treatments in non-pCR responders.

Keywords: PD-L1; TILs; breast cancer; neoadjuvant chemotherapy; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B7-H1 Antigen / biosynthesis*
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / surgery
  • CD8-Positive T-Lymphocytes / pathology*
  • Combined Modality Therapy
  • Female
  • Forkhead Transcription Factors / analysis
  • Humans
  • Kaplan-Meier Estimate
  • Lymph Node Excision
  • Lymphocytes, Tumor-Infiltrating* / chemistry
  • Mastectomy
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm, Residual
  • Prognosis
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / chemistry
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / surgery
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Neoplasm Proteins