Breast Cancer Research and Treatment

, Volume 162, Issue 1, pp 19–30 | Cite as

PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients

  • Julia Y. S. Tsang
  • Wai-Ling Au
  • Kwan-Yin Lo
  • Yun-Bi Ni
  • Thazin Hlaing
  • Jintao Hu
  • Siu-Ki Chan
  • Kui-Fat Chan
  • Sai-Yin Cheung
  • Gary M. Tse
Preclinical study



Clinical trials showing programmed death (PD)-1–PD-ligand 1 (L1) axis as a promising therapeutic target in melanoma and non-small cell lung cancers have made the pathway a focus of recent attention. However, the data regarding PD-L1/PD-1 in breast cancer are inconsistent. Given the heterogeneity of breast cancers, the clinical relevance of PD-L1 and PD-1 tumor infiltrating lymphocytes (TIL) may vary according to subtypes of breast cancer. We aim to investigate PD-L1 expression in a large cohort of breast cancers and analyze its clinico-pathological as well as outcome relationship according to molecular subtypes. Also, we evaluate the relationship of PD-1 TIL and PD-L1 expression with patients’ survival, particularly for breast cancers with high TIL.

Methods and results

Immunohistochemical analysis of PD-L1 on tissue arrays for 1091 breast cancer patients and PD-1 TIL on 97 whole sections was performed. Associations of PD-L1 with luminal cancers (p < 0.001) and features associated with that subtype [lower histologic grade, absence of necrosis, ER, PR, and AR expression (p < 0.001)] were observed. However, in HER2+ breast cancers, PD-L1 was an independent poor prognostic indicator (DFS: HR = 1.866, p = 0.001; OS: HR = 1.517, p = 0.036). Interestingly, HER2+ cancers showed a lower PD-1 TIL level compared to the other high TIL cases (p = 0.011). Cases with low PD-TIL but high PD-L1 expression showed the worst survival. This could be indicative of an active immune suppression by PD-L1 expression.


Our data showed the relevance of PD-L1 expression in HER2+ breast cancer. A combined evaluation of PD-L1 and PD-1 TIL in the prognosis of breast cancer might also be of value in treatment prediction.


Breast cancer subtype Programmed death ligand 1 Tumor infiltrating lymphocyte Immunohistochemistry Human epidermal growth factor receptor 2 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was performed in accordance with the ethical standards of CUHK-NETC CREC and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

No informed consent has been obtained as only archival materials from pathology tissue bank were retrieved after its use for diagnosis and the patients were non-identifiable. The research could be permissible without consent.

Supplementary material

10549_2016_4095_MOESM1_ESM.docx (1 mb)
Supplementary material 1 (DOCX 1063 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Julia Y. S. Tsang
    • 1
  • Wai-Ling Au
    • 1
  • Kwan-Yin Lo
    • 1
  • Yun-Bi Ni
    • 1
  • Thazin Hlaing
    • 2
  • Jintao Hu
    • 3
  • Siu-Ki Chan
    • 4
  • Kui-Fat Chan
    • 5
  • Sai-Yin Cheung
    • 5
  • Gary M. Tse
    • 1
  1. 1.Department of Anatomical and Cellular Pathology, Prince of Wales HospitalThe Chinese University of Hong KongShatinHong Kong
  2. 2.Department of Anatomic PathologyCentro Hospitalar Conde de Sao JanuarioMacao SARChina
  3. 3.Department of PathologyShenzhen People’s HospitalShenzhenChina
  4. 4.Department of PathologyKwong Wah HospitalYau Ma TeiHong Kong
  5. 5.Department of PathologyTuen Mun HospitalTuen MunHong Kong

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