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

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Abstract

Purpose

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.

Conclusions

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.

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Authors and Affiliations

  1. Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Ngan Shing Street, Shatin, NT, Hong Kong

    Julia Y. S. Tsang, Wai-Ling Au, Kwan-Yin Lo, Yun-Bi Ni & Gary M. Tse

  2. Department of Anatomic Pathology, Centro Hospitalar Conde de Sao Januario, Macao SAR, China

    Thazin Hlaing

  3. Department of Pathology, Shenzhen People’s Hospital, Shenzhen, 518020, China

    Jintao Hu

  4. Department of Pathology, Kwong Wah Hospital, Yau Ma Tei, Hong Kong

    Siu-Ki Chan

  5. Department of Pathology, Tuen Mun Hospital, Tuen Mun, Hong Kong

    Kui-Fat Chan & Sai-Yin Cheung

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  1. Julia Y. S. Tsang
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Correspondence to Gary M. Tse.

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All authors declare that they have no conflict of interest.

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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.

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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.

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Tsang, J.Y.S., Au, WL., Lo, KY. et al. PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients. Breast Cancer Res Treat 162, 19–30 (2017). https://doi.org/10.1007/s10549-016-4095-2

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