Plasma Proteomics for Biomarkers of Breast Cancer

Protein-based breast cancer biomarkers are a promising resource for breast cancer detection at the earliest and most treatable stages of the disease. Plasma is well suited to proteomic-based methods of biomarker discovery because it is easily obtained, is routinely used in the diagnosis of many diseases, and has a rich pro- teome. However, due to the vast dynamic range in protein concentration and the often uncertain tissue and cellular origin of plasma proteins, proteomic analysis of plasma requires special consideration compared with tissue and cultured cells. For example, when studies report an upregulation of IL-6 in the serum of breast cancer patients compared with control individuals, it is difficult to know whether this protein is released directly from the tumor or whether IL-6 upregulation is a systemic reaction to the tumor and released by nontumor tissues.

Biomarkers should be tissue specific in addition to being tumor specific. If cancer is detected, but not the tissue of origin, it may create problems, since searching for a suspected tumor will add undo stress to the patient and increased cost to the treatment. Finding tissue-specific tumor markers has thus far proven difficult. Many candidate biomarkers have been concurrently identified in numerous tumor types. This likely reflects that fact that 90% of all cancers are of epithelial origin and thus express many of the same proteins. It is probable that a panel of biomarkers will be required to establish tissue specificity rather than a single protein; this panel may or may not be independent of a tumor-specific panel of biomarkers. In addition, early detection biomarkers may need to be used in conjunction with other screening methods, such as mammography, where the tissue of origin is not in question.

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