Biomarker discordance: why it occurs and why it is important

Although the analysis of hormone receptors and HER-2/neu has usually been performed on primary tumors only, a growing body of evidence suggests that substantial discordance exists between primary and metastatic disease for estrogen receptors (30-40%) and HER-2/neu (10-30%). This discordance may reflect alterations in pathologic assessment techniques, changes between primary and metastatic breast cancer, differences within a heterogenous tumor, or the effect of treatment. The etiology of discordance is poorly understood and frequently may reflect tumor heterogeneity along with lack of standardized preanalytic and analytic variables. Standardization of diagnostic variables can improve diagnostic reproducibility. Because of the emergence of targeted hormonal and HER-2/neu therapies, tumor biomarkers assume a pivotal role in treatment decisions. The loss of sensitivity to hormones or HER-2/neu may suggest tumor resistance; whereas, the acquisition of hormone receptors and HER-2/neu provides potential new treatment targets which can improve overall patient outcomes.