The Role of MicroRNAs in HER2-Positive Breast Cancer: Where We Are and Future Prospective

SIMPLE SUMMARY: Breast cancer is the most diagnosed malignancy in woman worldwide and, despite the availability of new innovative therapies, it remains the first cause of death for tumor in woman. 20% of all breast cancer cases are HER2 positive, meaning that they are characterized by an aberrant expression of the growth factor receptor HER2. This receptor is involved in survival and proliferation mechanisms, conferring to this breast cancer subtype a particular aggressiveness. The introduction of anti-HER2 agents, such as trastuzumab, in the clinical practice, significantly improved the prognosis. However, a great portion of patients is not responsive to this therapy. Thus, cancer research is working to provide new tools to better manage HER2 positive breast cancers, such as biomarkers and therapeutic approaches. MicroRNAs could be used for these purposes. They are small molecules involved in almost all biological processes, including cancer promoting pathways. Researchers consider microRNAs as promising clinical tools because they are easily detectable and stable in both tissues and blood samples, and an increasing body of evidence supports their potential use as targets of therapy, prognostic and predictive biomarkers, or therapeutic agents. This review sums up the most recent scientific publications about microRNAs in HER2 positive breast cancer. ABSTRACT: Breast cancer that highly expresses human epidermal growth factor receptor 2 (HER2+) represents one of the major breast cancer subtypes, and was associated with a poor prognosis until the introduction of HER2-targeted therapies such as trastuzumab. Unfortunately, up to 30% of patients with HER2+ localized breast cancer continue to relapse, despite treatment. MicroRNAs (miRNAs) are small (approximately 20 nucleotides long) non-coding regulatory oligonucleotides. They function as post-transcriptional regulators of gene expression, binding complementarily to a target mRNA and leading to the arrest of translation or mRNA degradation. In the last two decades, translational research has focused on these small molecules because of their highly differentiated expression patterns in blood and tumor tissue, as well as their potential biological function. In cancer research, they have become pivotal for the thorough understanding of oncogenic biological processes. They might also provide an efficient approach to early monitoring of tumor progression or response to therapy. Indeed, changes in their expression patterns can represent a flag for deeper biological changes. In this review, we sum up the recent literature regarding miRNAs in HER2+ breast cancer, taking into account their potential as powerful prognostic and predictive biomarkers, as well as therapeutic tools.