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Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review

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Abstract

Purpose

Radiation therapy (RT) for triple-negative breast cancer (TNBC) treatment is currently delivered in the adjuvant setting and is under investigation as a booster of neoadjuvant treatments. However, TNBC radioresistance remains an obstacle, so new biomarkers are needed to select patients for any integration of RT in the TNBC therapy sequence. MicroRNAs (miRs) are important regulators of gene expression, involved in cancer response to ionizing radiation (IR) and assessable by tumor tissue or liquid biopsy. This systematic review aimed to evaluate the relationships between miRs and response to radiation in TNBC, as well as their potential predictive and prognostic values.

Methods

A thorough review of studies related to miRs and RT in TNBC was performed on PubMed, EMBASE, and Web of Science. We searched for original English articles that involved dysregulation of miRs in response to IR on TNBC-related preclinical and clinical studies. After a rigorous selection, 44 studies were chosen for further analysis.

Results

Thirty-five miRs were identified to be TNBC related, out of which 21 were downregulated, 13 upregulated, and 2 had a double-side expression in this cancer. Expression modulation of many of these miRs is radiosensitizing, among which miR-7, -27a, -34a, -122, and let-7 are most studied, still only in experimental models. The miRs reported as most influencing/reflecting TNBC response to IR are miR-7, -27a, -155, -205, -211, and -221, whereas miR-21, -33a, -139-5p, and -210 are associated with TNBC patient outcome after RT.

Conclusion

miRs are emerging biomarkers and radiosensitizers in TNBC, worth further investigation. Dynamic assessment of circulating miRs could improve monitoring and TNBC RT efficacy, which are of particular interest in the neoadjuvant and the high-risk patients’ settings.

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Abbreviations

APBI:

Accelerated partial breast irradiation

BC:

Breast cancer

CSC:

Cancer stem cells

DDR:

DNA damage repair

DFS:

Disease-free survival

DMFS:

Distant metastasis-free survival

EMT:

Epithelial–mesenchymal transition

ER:

Estrogen receptor

FFPE:

Formalin-fixed paraffin-embedded

IR:

Ionizing radiation

HR:

Homologous recombination

miR:

MicroRNA

NACT:

Neoadjuvant chemotherapy

OS:

Overall survival

pCR:

Pathological complete response

PTEN:

Phosphatase and tensin homolog

RT:

Radiation therapy

S1P:

Sphingosine-1-phosphatase

TCGA:

The Cancer Genome Atlas

TME:

Tumor microenvironment

TNBC:

Triple-negative breast cancer

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Acknowledgements

The authors would like to thank Ms. Myrna Perlmutter for her checking in English writing.

Funding

INCa (PROUST Project).

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Author notes

  1. Nina Radosevic-Robin and Yazid Belkacemi have equally contributed in this work.

Authors and Affiliations

  1. Radiation Oncology Department and Henri Mondor Breast Center, AP-HP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, 94010, Créteil, France

    Nhu Hanh To, Bisheng Liu & Yazid Belkacemi

  2. Department of Medical Oncology 4, Ho Chi Minh City Oncology Hospital, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam

    Hoang Quy Nguyen

  3. University of Paris-Est Créteil (UPEC), Créteil, France

    Allan Thiolat, José Cohen & Yazid Belkacemi

  4. INSERM Unit 955, Immunoregulation and Biotherapy (I-Biot) Team, Mondor Institute of Biomedical Research (IMRB), Créteil, France

    Nhu Hanh To, Allan Thiolat, José Cohen & Yazid Belkacemi

  5. Department of Pathology, Centre Jean Perrin, University Clermont Auvergne, INSERM U1240, Clermont-Ferrand, France

    Nina Radosevic-Robin

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  1. Nhu Hanh To
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On behalf of the TransAtlantic Radiation Oncology Network (TRONE) & Association of Radiotherapy, and Oncology of the Mediterranean Area (AROME)

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Correspondence to Yazid Belkacemi.

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To, N.H., Nguyen, H.Q., Thiolat, A. et al. Radiation therapy for triple-negative breast cancer: emerging role of microRNAs as biomarkers and radiosensitivity modifiers. A systematic review. Breast Cancer Res Treat 193, 265–279 (2022). https://doi.org/10.1007/s10549-022-06533-3

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  • DOI: https://doi.org/10.1007/s10549-022-06533-3

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