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Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies

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Abstract

Background

The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy.

Methods

We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate.

Results

Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096).

Conclusions

High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.

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Funding

Dr. Jing Zhao received research grant from National Natural Science Foundation of China (NSFC 81602320).

Author information

Authors and Affiliations

  1. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China

    Jing Zhao & Zhimin Wei

  2. Department of Hematology and Oncology, Emory University, Atlanta, GA, USA

    Jane Meisel

  3. Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA

    Yi Guo & Limin Peng

  4. Department of Pharmacology, Emory University, Atlanta, GA, USA

    Rita Nahta

  5. Department of Medicine, University of Wisconsin, Madison, WI, USA

    Ruth O’Regan

  6. Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA

    Kung Lin Hsieh & Xiaoxian Li

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  1. Jing Zhao
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Contributions

Conception and design: XL; Analysis and interpretation of data: JZ, YG, XL; Manuscript drafting and reviewing: All authors; XL is responsible for the overall content.

Corresponding author

Correspondence to Xiaoxian Li.

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Conflict of interest

Dr. Jane Meisel has been advisor for Puma and Pfizer and received research grants from Seattle Genetics, Pfizer and Lilly. Other authors declare that they have no conflict of interest.

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Zhao, J., Meisel, J., Guo, Y. et al. Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies. Breast Cancer Res Treat 183, 599–606 (2020). https://doi.org/10.1007/s10549-020-05819-8

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