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Breast cancer (BC) remains a widespread disease worldwide, despite advances in its detection and treatment. microRNAs (miRNAs) play a significant role in cancer, and their presence within exosomes may confer several advantages in terms of tumor initiation, propagation, immune evasion, and drug resistance compared to freely circulating miRNAs in the blood. The objective of this study was to conduct a systematic review to analyze the role of exosomal miRNAs present in serum or plasma as biomarkers in BC. Bibliographic sources were collected from various databases with no starting date limit until March 2023. The search terms used were related to "breast cancer," "microRNAs," and "exosomes." Following the search, inclusion and exclusion criteria were applied, resulting in a total of 46 articles. Data were extracted from the selected studies and summarized to indicate the miRNAs, type of dysregulation, sample source, number of patients and controls, and clinical relevance of the miRNAs. We carried out an enrichment study of the microRNAs that appeared in at least 3 studies, those that were suitable for selection were miR-16, miR-21 and miR-155. Exosomal miRNAs isolated from blood samples of patients diagnosed with BC could be valuable in the clinical setting. They could provide information about early diagnosis, disease progression, recurrence, treatment response, and metastases. It is crucial to reach a consensus on the specific exosomal miRNAs to detect and the most appropriate type of sample for comprehensive utilization of miRNAs as biomarkers for BC.
RESUMO
PURPOSE: HER2 overexpression in breast cancer correlates with poor outcomes. The incorporation of Trastuzumab into the treatment regimen has notably improved patient prognoses. However, cardiotoxicity emerges in approximately 20% of patients treated with the drug. This study aims to investigate the association between the HER2 655 A > G polymorphism, Trastuzumab-induced cardiotoxicity, and patient survival. METHODS: The study involved 88 patients treated with Trastuzumab. Cardiotoxicity, defined as a reduction in left ventricular ejection fraction (LVEF) from baseline or the emergence of clinical signs of congestive heart failure, was identified during treatment follow-up. Genotyping of HER2 655 A > G employed TaqMan SNP technology. RESULTS: Genotype frequencies of HER2/neu 655 (53 AA, 32 AG, and 3 GG) were consistent with Hardy-Weinberg equilibrium. No significant differences were observed in mean baseline LVEF between patients who developed cardiotoxicity and those who did not. Within these groups, neither AA nor AG genotypes showed an association with changes in mean baseline or reduced LVEF levels. Logistic regression analysis, adjusted for hormonal status and anthracycline treatment, revealed that AG genotype carriers face a significantly higher risk of cardiotoxicity compared to AA carriers (OR = 4.42; p = 0.037). No association was found between the HER2/neu 655 A > G polymorphism and disease-free or overall survival, regardless of whether the data was adjusted for stage or not. CONCLUSION: HER2 655 A > G polymorphism is significantly linked to an increased risk of Trastuzumab-induced cardiotoxicity but does not correlate with variations in disease-free survival or overall survival rates.
RESUMO
PURPOSE: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. METHODS: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. RESULTS: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. CONCLUSION: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.