Analysis of gene expression patterns governing these events has resulted in the classification of breast tumors into subtypes broadly determined by expression of the estrogen receptor, progesterone receptor and human epidermal growth factor receptor. Targeted therapies including hormonal therapy for ER positive tumors and trastuzumab to inhibit HER2/neu signaling have become the major components of adjuvant breast cancer management. Consequently, when diagnosed and treated early, breast cancer is highly curable. Despite these advances, hematogenous spread of malignant cells from the primary tumor to distant organs with subsequent proliferation into metastases remains the leading cause of death for breast cancer patients. Further insight into the molecular mechanisms underlying tumorigenic transformation is clearly warranted for the identification of additional molecular predictors and AZ 960 disease biomarkers in the clinical management of breast cancer. Much current cancer research is focused on the identification of circulating cancer-specific biomarkers for application to disease diagnostics, as well as predicting and monitoring response to disease and tumor recurrence. There are no reliable circulating biomarkers for breast cancer. Mammography is the most widespread screening tool, with a definitive diagnosis requiring an invasive tissue biopsy. This prevalent disease is in need of a minimally invasive biomarker which may be used in combination with radiological imaging to facilitate early subtype specific tumor diagnosis. Blood presents an excellent medium for biomarker discovery; it is minimally invasive and simple to obtain during routine clinical examination. Moreover, blood circulates throughout the body delivering nutrients and carrying proteins, hormones and cells while eliminating waste substances, thereby reflecting the summation of physiological and pathological processes occurring in an individual at any one time. MiRNAs have shown much potential as cancer-specific biomarkers. MiRNAs regulate gene expression at the posttranscriptional level and are intimately linked with the cancer state; Firstly, miRNA expression has a causal effect on tumourigenesis, acting as oncogenes and tumor suppressor genes and secondly, altered miRNA expression occurs as a result of the carcinogenic process. In breast cancer, altered tissue miRNA expression patterns have been shown to correlate with molecular subtype and hormonal receptor status. MiRNAs were originally studied in tissue, but several studies have demonstrated that tumor-specific miRNAs are detectable in the circulation. These studies allude to the promising role of circulating miRNAs as biomarkers for detection of disease. Furthermore, speculation that circulating miRNA profiles could reflect not only the tumor tissue-type, but also the intrinsic molecular subtype thus acting as a fluid biopsy would be particularly valuable in breast cancer where management, even immediately following diagnosis, is governed by hormonal and HER2/neu receptor status, largely conveying molecular subtype. Luminal A is the most common subtype, including over 70% of breast cancers. Confirmation of Luminal A subtype is performed using mRNA expression analysis however phenotypically Luminal A-like tumors are characterized as hormone receptor positive and HER2/neu negative.
With distinct tumor phenotypes reflecting a spectrum of underlying molecular alterations and initiating events
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