Analysis of RANK/RANKL expression in metastatic and non-metastatic breast cancer: Systematic literature review

Authors

DOI:

https://doi.org/10.33448/rsd-v14i3.48399

Keywords:

RANK Ligand, RANK Protein, Neoplasm Metastases, Breast Cancer, Prognosis, Survival.

Abstract

Breast cancer is the most frequent cause of death from cancer in the female population worldwide and the clinical management of these patients represents a challenge, given the variety of disease progression profiles. The presence of distant metastasis has a major impact on patient survival, with bone metastases being the most common. The RANK/RANKL/OPG system is identified as a signaling pathway involved in the maintenance of bone homeostasis and mammary gland development. The investigation of the association between the biomarkers expression of receptor activator of nuclear factor kappa B (RANK) and binding protein (RANKL) in the prognostic and predictive assessment of breast cancer helps in the discussion of the use of denosumab in the prevention of bone metastases and in the treatment of the disease. This study aims to present a systematic review on the analysis of RANK/RANKL expression in metastatic and non-metastatic breast cancer. Eight studies totaling 1876 patients were included, and six of the studies demonstrated associations between the occurrence of more aggressive tumors, the metastatic potential of breast cancer, the emergence of bone metastases and, mainly, a worse prognosis in survival curves. The studies included in this review confirm the predictive and prognostic importance of RANK in the evaluation of patients with breast cancer, reaffirming the need for more homogeneous studies for the adequate use of therapeutic and preventive protocols that use this marker as a therapeutic target.

Downloads

Download data is not yet available.

References

Abreu, C., et al. (2022). Exploring new pathways in endocrine-resistant breast cancer. Exploration of Targeted Anti-tumor Therapy, 3, 337–361.

Azim, H. A., et al. (2015). RANK-ligand (RANKL) expression in young breast cancer patients and during pregnancy. Breast Cancer Research, 17(1).

Buitrago, F., et al. (2011). Fatores prognósticos em câncer de mama. Comunicação em Ciências da Saúde, 69–81.

Hortobagyi, G. N., et al. (2017). AJCC cancer staging manual. Springer International Publishing.

Ibrahim, T., et al. (2011). Role of RANK, RANKL, OPG, and CXCR4 tissue markers in predicting bone metastases in breast cancer patients. Clinical Breast Cancer, 11(6), 369–375.

Infante, M., et al. (2019). RANKL/RANK/OPG system beyond bone remodeling: Involvement in breast cancer and clinical perspectives. Journal of Experimental and Clinical Cancer Research, 28.

Instituto Nacional de Câncer José Alencar Gomes da Silva. (2023). Estimativa 2023: incidência de câncer no Brasil. INCA.

International Agency for Research on Cancer. (2020). Cancer today. WHO.

Kiesel, L., & Kohl, A. (2016). Role of the RANK/RANKL pathway in breast cancer. Maturitas, 86, 10–16.

Li, R., et al. (2015). The RANK pathway in advanced breast cancer: Does Src play a role? Disponível em: http://www.r-project.org.

Mamédio, C., et al. (n.d.). The PICO strategy for the research question construction and evidence search. Revista Latino-Americana de Enfermagem. Disponível em: www.eerp.usp.br/rlae. Acessado em 7 de junho de 2023.

Page, M. et al. (2021). The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PMJ. 372 (71). doi: https://doi.org/10.1136/bmj.n71.Park, H. S., et al. (2014). Expression of receptor activator of nuclear factor kappa-B as a poor prognostic marker in breast cancer. Journal of Surgical Oncology, 807–812.

Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Editora UAB/NTE/UFSM.

Pfitzner, B. M., et al. (2014). RANK expression as a prognostic and predictive marker in breast cancer. Breast Cancer Research and Treatment, 145(2), 307–315.

Rang, H. P., et al. (2016). Rang & Dale: Farmacologia (8ª ed.). Editora Elsevier.

Santini, D., et al. (2011). Receptor activator of NF-kB (RANK) expression in primary tumors associates with bone metastasis occurrence in breast cancer patients. PLoS One, 6(4).

Santos, C. M. C. (2007). A estratégia PICO para a construção da pergunta de pesquisa e busca de evidências. Rev. Latino-Am. Enfermagem 15 (3). https://doi.org/10.1590/S0104-11692007000300023.

Silva, I., & Branco, J. C. (2011). Rank/Rankl/Opg: literature review. Acta Reumatológica Portuguesa, 36(3), 209–218.

Zhang, L., et al. (2012). Receptor activator for nuclear factor κ B expression predicts poor prognosis in breast cancer patients with bone metastasis but not in patients with visceral metastasis. Journal of Clinical Pathology, 65(1), 36–40.

Zhang, L., et al. (2015). The E3 ubiquitin ligase Cbl-b improves the prognosis of RANK positive breast cancer patients by inhibiting RANKL-induced cell migration and metastasis. Oncotarget, 6(26), 22918–22933.

Published

2025-03-06

Issue

Section

Health Sciences

How to Cite

Analysis of RANK/RANKL expression in metastatic and non-metastatic breast cancer: Systematic literature review. Research, Society and Development, [S. l.], v. 14, n. 3, p. e0914348399, 2025. DOI: 10.33448/rsd-v14i3.48399. Disponível em: https://ojs34.rsdjournal.org/index.php/rsd/article/view/48399. Acesso em: 28 jun. 2025.