miRNAs as emerging predictors of tamoxifen resistance in breast cancer.

Abstract

One of the most common cancers among women worldwide is breast cancer (BC). Many BC patients express estrogen receptors (ER), and estrogens are critical for their survival, development, and invasion. Therefore, the ability to produce and respond to estrogen, known as endocrine function, represents a potential drug treatment for ER-positive BC. Tamoxifen (TAM), a selective ER modulator, is widely used in hormone-based therapy. However, the emergence of TAM resistance is a significant clinical challenge that often leads to recurrence, progression, and metastasis. Despite its importance, there are currently no reliable biomarkers to predict patient response to hormone-based therapies. MicroRNAs (miRNAs), small non-coding RNAs, have emerged as key regulators in various physiological and pathological processes, including BC initiation, progression, and resistance to therapy. Recent studies highlight the potential of specific miRNAs as predictive biomarkers for TAM resistance. Notably, miR-382-3p and miR-93 are significantly upregulated in TAM-resistant patients, while miR-182-3p is increased in TAM-sensitive patients. Other studies have also shown that circulating miR-221/222 expression can predict recurrence and resistance to tamoxifen treatment in BC patients. Therefore, testing miR-221/222 expression in patients with ductal BC undergoing tamoxifen treatment is recommended to rapidly identify the risk of tamoxifen resistance and enhance treatment efficacy. These findings emphasize the diagnostic and prognostic potential of miRNAs in BC, especially in identifying patients at risk of developing resistance to hormone-based therapies, and provide insights that could enhance personalized treatment strategies and improve treatment outcomes for BC patients.