# An Emerging Role of Long Noncoding RNAs as Novel Biomarkers for Breast Cancer Metastasis
## 3 Molecular and Functional Insights into Breast Cancer Metastasis  
### Mutational Background of Breast Cancer  
BC is characterized by a heterogeneous and complex mutational landscape that significantly influences its development, progression, and clinical behavior. This landscape encompasses a wide range of genetic alterations, including point mutations, insertions, deletions, copy number variations, and chromosomal rearrangements. These mutations can occur in oncogenes, tumor suppressor genes, and genes involved in DNA repair, contributing to the diversity of BC subtypes and their responses to therapy. One of the most well-studied aspects of BC genetics is the presence of mutations in the BRCA1 and BRCA2 genes, which are crucial for DNA repair through homologous recombination. Germline mutations in these high-penetrance genes significantly increase the risk of developing BC and are associated with hereditary breast and ovarian cancer syndromes. BRCA1/2 mutations often lead to defects in DNA repair mechanisms, resulting in genomic instability and a higher likelihood of accumulating additional mutations that drive tumorigenesis [7]. Mutations in other high-penetrance genes such as TP53, PTEN, PALB2, and CHEK2 also contribute to hereditary breast cancer syndromes, each implicating distinct molecular pathways in tumorigenesis [8]. For example, TP53 mutations, which are common in TNBC, lead to the loss of its function in regulating cell cycle arrest, apoptosis, and genomic stability, thereby promoting cancer cell survival and proliferation [9]. In addition to germline mutations, somatic mutations acquired during the patient's lifetime further complicate the genomic architecture of BC. These mutations frequently involve key oncogenes and tumor suppressor genes, including PIK3 CA, TP53, and HER2, driving oncogenic signaling pathways, genomic instability, and tumor heterogeneity. PIK3 CA mutations are prevalent in hormone receptor-positive BC and predict responsiveness to PI3K inhibitors, while HER2 amplifications inform the use of HER2-targeted therapies [10]. The mutational landscape also includes alterations in genes such as GATA3, MAP3K1, CDH1, and PTEN, each contributing to various oncogenic processes. For instance, mutations in GATA3, a transcription factor involved in luminal cell differentiation, are prevalent in the luminal A subtype of BC and are associated with better prognosis. Conversely, PTEN mutations, leading to the activation of the PI3K/AKT pathway, are often found in more aggressive forms of BC and are linked to unfavorable outcomes [11].  
LncRNAs play a pivotal role in modulating the effects of genetic mutations and contribute to the complexity of the mutational landscape in BC. These lncRNAs can interact with mutated genes and pathways, influencing their expression and activity. As discussed in subsequent sections of this review, lncRNAs can impact the behavior of mutated oncogenes and tumor suppressor genes, thereby altering the progression and characteristics of BC. This intricate interplay between lncRNAs and genetic mutations underscores the importance of understanding lncRNA functions in the context of BC pathogenesis [12].