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Radiosensitivity is associated with antitumor immunity in estrogen receptor-negative breast cancer

  • Preclinical Study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

This study evaluated radiosensitivity and the tumor microenvironment (TME) to identify characteristics of breast cancer patients who would benefit most from radiation therapy.

Methods

We analyzed 1903 records from the Molecular Taxonomy of Breast Cancer International Consortium cohort using the radiosensitivity index and gene expression deconvolution algorithms, CIBERSORT and xCell, that estimates the TME composition of tumor samples. In this study, patients were stratified according to TME and radiosensitivity. We performed integrative analyses of clinical and immuno-genomic data to characterize molecular features associated with radiosensitivity.

Results

Radiosensitivity was significantly associated with activation of antitumor immunity. In contrast, radioresistance was associated with a reactive stromal microenvironment. The immuno-genomic analysis revealed that estrogen receptor (ER) pathway activity was correlated with suppression of antitumor immunity. In ER-negative disease, the best prognosis was shown in the immune-high and radiosensitive group patients, and the lowest was in the immune-low and radioresistant group patients. In ER-positive disease, immune signature and radiosensitivity had no prognostic significance.

Conclusion

Taken together, these results suggest that tumor radiosensitivity is associated with activation of antitumor immunity and a better prognosis, particularly in patients with ER-negative breast cancer.

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Data availability

The data generated in this study are publicly available.

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Funding

This work was supported by grants from the Ministry of Science and Information & Communication Technology (NRF#2020R1A2C2005141).

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Authors and Affiliations

  1. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Byung-Hee Kang & In Ah Kim

  2. Department of Radiation Oncology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Bum-Sup Jang

  3. Department of Radiation Oncology and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea

    In Ah Kim

Authors
  1. Byung-Hee Kang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by B-HK. The first draft of the manuscript was written by B-HK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to In Ah Kim.

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The authors declare no competing interests.

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Institutional review board (IRB) approval at Seoul National University Bundang Hospital was waived as publicly available databases were used.

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Kang, BH., Jang, BS. & Kim, I.A. Radiosensitivity is associated with antitumor immunity in estrogen receptor-negative breast cancer. Breast Cancer Res Treat 197, 479–488 (2023). https://doi.org/10.1007/s10549-022-06818-7

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  • DOI: https://doi.org/10.1007/s10549-022-06818-7

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