Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.

Extracellular vesicles (EVs), ubiquitously released by blood cells, facilitate intercellular communication. In cancer, tumor-derived EVs profoundly affect the microenvironment, promoting tumor progression and raising the risk of recurrence. These EVs contain miRNAs (EV-miRNAs), promising cancer biomarkers. Characterizing plasma EVs and identifying EV-miRNAs associated with breast cancer recurrence are crucial aspects of cancer research since they allow us to discover new biomarkers that are effective for understanding tumor biology and for being used for early detection, disease monitoring, or approaches to personalized medicine. This study aimed to characterize plasma EVs in breast cancer (BC) patients and identify EV-miRNAs associated with BC recurrence. This retrospective observational study included 24 BC patients divided into recurrence (n= 11) and non-recurrence (n= 13) groups. Plasma EVs were isolated and characterized. Total RNA from EVs was analyzed for miRNA expression using NanoString's nCounter® miRNA Expression Assays panel. MicroRNA target prediction used mirDIP, and pathway interactions were assessed via Reactome. A stronger presence of circulating EVs was found to be linked with a less favorable prognosis (p = 0.0062). We discovered a distinct signature of EV-miRNAs, notably including miR-19a-3p and miR-130b-3p, which are significantly associated with breast cancer recurrence. Furthermore, miR-19a-3p and miR-130b-3p were implicated in the regulation of PTEN and MDM4, potentially contributing to breast cancer progression. A notable association emerged, indicating a high concentration of circulating EVs predicts poor prognosis (p = 0.0062). Our study found a distinct EV-miRNA signature involving miR-19a-3p and miR-130b-3p, strongly associated with disease recurrence. We also presented compelling evidence for their regulatory roles in PTEN and MDM4 genes, contributing to BC development. This study revealed that increased plasma EV concentration is associated with BC recurrence. The prognostic significance of EVs is closely tied to the unique expression profiles of miR-19a-3p and miR-130b-3p. These findings underscore the potential of EV-associated miRNAs as valuable indicators for BC recurrence, opening new avenues for diagnosis and treatment exploration.

High-grade cervical intraepithelial lesions (CIN 2/3) are critical targets for early detection in cervical cancer prevention. MicroRNAs are stable, tissue-specific molecules involved in cancer-related pathways and can be detected in minimally invasive samples, making them suitable for use in the context of liquid biopsies. This exploratory study aimed to identify differentially expressed microRNAs in paired liquid-based cytology (LBC) and plasma samples from women with CIN 2/3, and to evaluate miR-339-3p as a potential biomarker. Samples from 70 women (35 cases with histologically confirmed high-grade lesions and 35 age-matched controls with normal cytology and negative HPV tests) were analyzed using a commercial microRNA panel on the NanoString platform. We identified 57 dysregulated microRNAs in LBC samples and 33 in plasma, with four shared between both matrix types. Among these, miR-339-3p was the only one consistently upregulated and significantly associated with case status. In LBC samples, the area under the curve was 0.65; in plasma, 0.64. Pathway analysis suggested its involvement in apoptosis-related pathways, including PI3K-Akt and p53. Moreover, this study highlights the value of integrating microRNA profiling across local and systemic samples to advance biomarker discovery in cervical cancer.

Liquid biopsy offers a minimally invasive approach for cancer diagnosis by detecting circulating biomarkers, such as microRNAs (miRNAs), in different types of specimens. The present study aimed to identify the most effective specimen for miRNA detection in cervical cancer precursor lesions by comparing plasma, urine and liquid‑based cytology (LBC). A total of 798 miRNAs were analyzed using NanoString technology in 24 women, equally divided between those with high‑grade cervical intraepithelial neoplasia (2/3) and controls with negative Pap and human papillomavirus tests. Comparative analyses revealed that LBC exhibited the highest detection efficiency, with only 1.75% of miRNAs demonstrating low counts, compared with 20.68% in plasma and 15.79% in urine. Additionally, LBC exhibited 21.3% of miRNAs above the 9th decile of expression, compared with 5.89% in plasma and 2.88% in urine. LBC revealed the most consistent detection performance across samples, establishing its potential as the most effective specimen for detecting cervical cancer precursor lesions biomarkers. Plasma also showed promise as a detection medium, whilst urine exhibited higher variability and lower detection consistency. In conclusion, LBC demonstrated the highest efficacy for miRNA detection among the specimen types tested. Plasma remains a viable alternative, whilst urine presents challenges due to its inherent variability. These results underscore the importance of specimen selection for optimizing diagnostic sensitivity in cervical cancer precursor lesions screening.

MicroRNAs (miRNAs) have been associated with the initiation, development, and progression of various cancers, including cervical cancer. Their involvement in cervical cancer is extensively documented, as they influence critical biological pathways, including apoptosis, cell cycle progression, immune evasion, and metastasis. In cervical cancer, deregulated miRNA expression contributes to tumor aggressiveness by interfering with key molecular pathways, many of which are also influenced by high-risk human papillomavirus (HPV) oncoproteins. In this review, we highlight key signaling pathways regulated by miRNAs linked to cancer hallmarks, particularly sustained proliferative signaling, which was the most frequently affected pathway across the studies reviewed. Furthermore, the interplay among HPV oncoproteins, dysregulated miRNA expression, and altered signaling pathways drives key oncogenic processes, including uncontrolled proliferation, evasion of apoptosis, and metastasis.

Breast cancer is a leading cause of central nervous system (CNS) metastases in women, often associated with poor prognosis and limited therapeutic options. However, molecular differences between primary tumors and CNS metastases remain underexplored. We aimed to characterize transcriptomic differences between primary breast tumors and matched CNS metastases and identify immune-related biomarkers associated with metastatic progression and patient outcomes. Transcriptomic profiling was based on 11 matched FFPE sample pairs (primary tumor and CNS metastasis). Paired formalin-fixed paraffin-embedded (FFPE) samples from primary tumors (T1) and CNS metastases (T2) were analyzed using the NanoString nCounter^® platform and the PanCancer IO 360™ Gene Expression Panel. Differential gene expression, Z-score transformation, and heatmap visualization were performed in R. In silico survival analyses for overall survival (OS) and recurrence-free survival (RFS) were conducted using publicly available TCGA and GEO datasets. Forty-five genes were significantly differentially expressed between the T1 and T2 samples. Immune-related genes such as CXCL9, IL7R, CD79A, and CTSW showed consistent downregulation in CNS metastases. High expression of CXCL9 and CD79A was associated with improved OS and RFS, whereas high IL7R and CTSW expression correlated with worse outcomes. These findings indicate immune suppression as a hallmark of CNS colonization. Comparative transcriptomic analysis further underscored the distinct molecular landscapes between primary and metastatic tumors. This study highlights transcriptional signatures associated with breast cancer CNS metastases, emphasizing the role of immune modulation in metastatic progression. The identified genes have potential as prognostic biomarkers and therapeutic targets, supporting the need for site-specific molecular profiling in metastatic breast cancer management.