microRNA-221 and tamoxifen resistance in luminal-subtype breast cancer patients: A case-control study

Abstract

Background Around 70% of breast cancers (BCs) are estrogen receptor-α (ERα)-positive. Adjuvant endocrine therapy is used to reduce estrogen levels and inhibit signal transduction through the ER. The anti-estrogen drugs that are most commonly used in endocrine therapy belong to the selective ER modulator (SERM) class and include tamoxifen. Although it has been used for three decades in cases of early-stage and ERα-positive BC, resistance to tamoxifen is a common problem. microRNAs (miRNAs) have a potential role in demonstrating BC resistance to tamoxifen therapy. Hence, there is a need to investigate the expression of miRNA-221 (miR-221) in luminal-subtype BC patients receiving tamoxifen therapy. Methods This case-control study investigated luminal-subtype BC patients who had undergone endocrine therapy for at least 1 year. The case group comprised patients with local or metastatic recurrence, and the control group comprised patients without local or metastatic recurrence. Results There was a significant difference in miR-221 expression ( p = 0.005) between the case and control groups. There were no significant differences between the groups that were positive and negative for the progesterone receptor (PR) ( p = 0.25), had high and low marker of proliferation Ki-67 levels ( p = 0.60), were positive and negative for lymphovascular invasion ( p = 0.14), and had stage 2 and stage 3 cancer ( p = 0.25). Conclusion miR-221 expression was higher in tamoxifen-resistant BC cases. miR-221 is a potential biomarker of tamoxifen resistance.

Glutamine synthetase regulates the immune microenvironment and cancer development through the inflammatory pathway

“…In particular, recent studies report that miRNAs contributed to the progression of breast cancer after tamoxifen treatment. The mechanisms include the activation of estrogen receptor alpha (ERα), progression of the cell cycle, regulation of apoptosis, and controlling epithelial-to-mesenchymal transition [68][69][70][71]. For these reasons, studies of differentially expressed miRNAs (DEMs) are similar to the research of differentially expressed genes (DEGs) to improve the susceptibility of tamoxifen against breast cancer and provide novel insights for clinical doctors.…”

p53 Mutation as Plausible Predictor for Endocrine Resistance Therapy in Luminal Breast Cancer

“…Distinguished studies also showed us that numerous studies of non-coding RNA especially miRNA play important roles in ET resistance, such as miRNA such as miRNA-1972, miRNA-375 and miRNA-221. 52,88 However there are still no clear depiction of p53 roles in ET resistance caused by miRNA involvement. It is due to the complexity of the network of both parties, in which miRNA could regulate p53 level and function and vice versa mutated p53 could regulate the miRNA expression and modulate miRNA biology activities due to its gain-of-function properties.…”

“…Distinguished studies also showed us that numerous studies of non-coding RNA especially miRNA play important roles in ET resistance, such as miRNA such as miRNA-1972, miRNA-375 and miRNA-221. 52 , 88 …”

Obesity as a Risk Factor for Breast Cancer—The Role of miRNA

“…miR-221 can be considered a potential biomarker of tamoxifen resistance. It was shown in a case-control study that serum miR-221 expression level is higher in tamoxifen-resistance luminal-subtype breast cancer patients with local recurrence and metastasis than in patients without progression [ 191 ]. Additionally, the inhibition of miR-221 and miR-222 restored the sensitivity of tamoxifen-resistant breast cancer cell line (MCF-7 TamR) cells to tamoxifen [ 192 ].…”