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Article Open Access

Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer

  • Authors:
    • Junnan Xu
    • Hua Bao
    • Xue Wu
    • Xiaonan Wang
    • Yang W. Shao
    • Tao Sun
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Key Laboratory of Liaoning Breast Cancer Research, Shenyang, Liaoning 110042, P.R. China, Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON M5G 1L7, Canada, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu 210032, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 449-455
    |
    Published online on: April 30, 2019
       https://doi.org/10.3892/ol.2019.10287
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Abstract

Immunotherapy has been found to be efficient in a variety of cancers and, therefore, may be a promising strategy for breast cancer (BC), particularly due to the limited therapeutic options currently available for triple‑negative BC (TNBC). However, heterogeneity of tumor mutation burden (TMB), immune gene expression and mismatch repair (MMR) gene activity across BC subtypes has not been well characterized. In the present study, a comprehensive analysis of TMB, expression levels of immune cell type marker genes, and expression levels of MMR‑associated genes was performed. A total of 5 MMR‑associated genes, including MLH1, MLH3, MSH2, MSH6 and PMS2, were analyzed. Patients that harbored at least two MMR genes with expression levels in the lower 10% percentile across the cohort were considered as potentially aberrant (lost expression). Hormone receptor (HR)‑negative BC is associated with a higher TMB and immune gene expression compared with HR‑positive BC [TMB, estrogen receptor (ER)‑negative vs. ER‑negative, 55 vs. 32, respectively; P=4.1x10‑13; progesterone receptor (PR)‑negative vs. PR‑positive, 53 vs. 31, respectively; P<2.2x10‑16]. By contrast, human epidermal growth factor receptor 2 (HER2)‑negative BC tended to have a lower TMB and decreased immune gene expression compared with HER2‑positive BC (TMB, HER2‑negative vs. HER2‑positive, 36 vs. 48, respectively; P=0.02). Furthermore, aberrant expression of MMR genes was found to be more common in HR‑negative compared with HR‑positive BC (P<0.001). Significantly higher expression levels of each immune marker gene of four major immune cell types were found in patients who were HR‑negative compared with patients who were HR‑positive (P<0.001). The findings of the present study suggest that HR‑negative or HER2‑positive BC exhibits elevated TMB and immunogenic activity, and immunotherapeutic options are recommended.
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Copy and paste a formatted citation
Spandidos Publications style
Xu J, Bao H, Wu X, Wang X, Shao YW and Sun T: Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer. Oncol Lett 18: 449-455, 2019.
APA
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y.W., & Sun, T. (2019). Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer. Oncology Letters, 18, 449-455. https://doi.org/10.3892/ol.2019.10287
MLA
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y. W., Sun, T."Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer". Oncology Letters 18.1 (2019): 449-455.
Chicago
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y. W., Sun, T."Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer". Oncology Letters 18, no. 1 (2019): 449-455. https://doi.org/10.3892/ol.2019.10287
Copy and paste a formatted citation
x
Spandidos Publications style
Xu J, Bao H, Wu X, Wang X, Shao YW and Sun T: Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer. Oncol Lett 18: 449-455, 2019.
APA
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y.W., & Sun, T. (2019). Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer. Oncology Letters, 18, 449-455. https://doi.org/10.3892/ol.2019.10287
MLA
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y. W., Sun, T."Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer". Oncology Letters 18.1 (2019): 449-455.
Chicago
Xu, J., Bao, H., Wu, X., Wang, X., Shao, Y. W., Sun, T."Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor‑negative or human epidermal growth factor receptor 2‑positive breast cancer". Oncology Letters 18, no. 1 (2019): 449-455. https://doi.org/10.3892/ol.2019.10287
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