HER2 status is an important biomarker in guiding personalized HER2 therapy

The human epidermal growth factor receptor (HER)2 oncoprotein has emerged as an important cellular target for the development of a variety of new cancer therapies. The method used to define the HER2 status is a major factor in determining who will receive these targeted therapies. The HER2 status can be determined by using either tissue tests to look at the primary tumor cells, or an enzyme-linked immunosorbent assay (ELISA) that measures the circulating levels of the extracellular portion of HER2 protein. Tissue test (immunohistochemistry and fluorescence in situ hybridization) results indicate that approximately 20-30% of patients with primary breast cancer have a HER2-positive tumor, whereas ELISA results demonstrate that an average of 45% (range: 23-80%) of metastatic breast cancer (MBC) patients can have an abnormally high (> 15 ng/ml) serum HER2 level, which is evidence that a HER2-positive tumor is present. Published studies show that the HER2 status of a breast cancer patient can differ both by the test method used and the time at which HER2 status is assessed. In this review, data will be shown that demonstrates that not all HER2 test results obtained from the primary breast cancer are correct, and that there is a population of patients categorized as HER2 negative by tissue tests that, in fact, have HER2-positive tumors. This observation has important therapeutic implications for breast cancer patients with HER2-positive tumors that are classified as HER2 negative, since they are not eligible for anti-HER2 therapy, such as trastuzumab. If a patient is found to have an elevated (> 15 ng/ml) serum HER2 level in MBC, then either the original tumor should be re-evaluated for HER2 status, or a metastatic lesion should be tested for HER2 positivity, to determine if the patient is eligible for anti-HER2 therapy. Studies have also shown that lack of adequate validation of a testing method can result in false conclusions concerning the HER2 status. If the goal of personalized medicine is to deliver the right treatment to the right patient at the right time then we need to ensure the validity of all test methods, regardless of whether they are for research purposes or are registered as in vitro diagnostics. In the case of establishing HER2 status, it takes more than one type of test to identify patients with HER2-positive tumors. It is highly likely that the introduction of additional targeted drugs to growth factor receptors or to angiogenesis targets will take a variety and combinations of tests to tailor the most appropriate therapy to the patient.