RESUMO
Breast cancer (BC) remains the most prevalent tumor and the leading cause of death among women worldwide, despite the advancements in diagnosis and new treatments. A significant challenge in BC treatment is the acquired or de novo resistance of tumors to systemic therapy. To overcome this obstacle, personalized treatment is needed, with a focus on finding biomarkers capable of predicting the response to therapy. MicroRNAs (miRNAs) have emerged as potential markers due to their diverse clinical applications. AIM: To examine the potential prognostic significance of miR-125b-2, -155, -221, and -320a expression in the tumor cells of individuals with hormone-dependent BC before undergoing neoadjuvant hormonal therapy. MATERIALS AND METHODS: The study is based on a retrospective analysis of the treatment outcome of 56 patients with stage II-III locally disseminated hormone-dependent BC. The real-time quantitative reverse transcription polymerase chain reaction was performed on the biopsy material to assess the expression of miR-125b-2, -155, and -221 before neoadjuvant hormonal therapy with aromatase inhibi- tor letrozole to predict clinical response. RESULTS: Most HER2/neu+ BC patients had low levels of miR-155 and miR-221 expression in tumor biopsy specimens. Tumors that responded well to letrozole exhibited lower levels of miR-125b-2 and miR-221 compared to non-responsive tumors. CONCLUSIONS: miR-125b-2, -155, and -221 expres- sion can predict resistance to the letrozole treatment of BC.
Assuntos
Neoplasias da Mama , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Letrozol/uso terapêutico , Estudos Retrospectivos , Hormônios/uso terapêutico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Hormonal therapy is one of the main methods of comprehensive treatment of patients with locally advanced breast cancer (BC). Despite the intensive search for molecules associated with the aggressiveness of the tumor process, currently there are no reliable markers predicting response to neoadjuvant hormonal therapy (NHT). AIM: To investigate the correlation between miR-125b-2, -155, -221, -320a expression in tumor tissue and HER2/neu status and response to tamoxifen treatment in BC patients. MATERIALS AND METHODS: Expression levels of miR-125b-2, -155, -221, and -320a were analyzed in biopsy samples of 50 BC patients using a real-time polymerase chain reaction. RESULTS: We found that levels of miR-125b-2, -155, -221, and -320a were 1.72, 1.65, 1.85, and 2.89 times higher in BC biopsy samples expressing estrogen/progesterone receptors and HER2/neu compared with HER2/neu-negative luminal tumors. Patients with a luminal BC showing higher levels of miR-125b-2 and miR-320a expression before therapy demonstrated better response to NHT with tamoxifen. A strong correlation was calculated for miR-221 expression and response to NHT (r = 0.61). CONCLUSIONS: The high levels of miR-125b-2, -155, -221, and -320a in tumor tissue are associated with the HER2/neu-positive status of luminal BC subtypes. Tumor samples of patients showing the low response to NHT with tamoxifen are characterized by lower expression of miR-125b-2 and -320a. Hence, miR-125b-2 and -320a could be considered as putative predictive biomarkers associated with tamoxifen sensitivity of hormone-dependent BC.