Potential Epigenetic Modifications Implicated in Triple- To Quadruple-Negative Breast Cancer Transition: A Review

Abstract

Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

Plain language summary

When the androgen hormone receptor becomes inactive in triple-negative breast cancer (TNBC) patients, it results in another subtype of breast cancer called quadruple-negative breast cancer (QNBC). This is because these patients already lack the biological activities of three other important hormone receptors. The functions of these receptors are targeted by some drugs used in the management of breast cancers, so the lack of these receptors in TNBC and QNBC patients is thought to be linked with poor response to treatment. Some epigenetic modifications are involved in a more severe disease that is very difficult to control in TNBC patients and could facilitate its transition to the more aggressive QNBC subtype. Treatment response could be improved by restoring the normal function of the altered genes by reversing the observed epigenetic alterations.

Graphical abstract

Keywords::

• epigenetic modifications
• genes
• quadruple-negative breast cancer
• therapeutic targets
• triple-negative breast cancer

Acknowledgments

The authors wish to acknowledge the enabling environment granted by the Department of Biochemistry, Ahmadu Bello University Zaria, Kaduna State, Nigeria, ensure the successful conduct of this critical review manuscript with global impact.

Financial & competing interests disclosure

C Yates received consultant/honorarium from Amgen, QED Therapeutics and Riptide Biosciences and is an owner of stock in Riptide Biosciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Data availability statement

Data will be provided on request.

Additional information

Funding

C Yates received consultant/honorarium from Amgen, QED Therapeutics and Riptide Biosciences and is an owner of stock in Riptide Biosciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.