Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy.

The estrogen receptor (ER) is a regulator of cellular growth, proliferation, and differentiation. In addition to having prognostic value, ER is the most important biologic marker of therapeutic response in breast cancer. Some level of measurable ER protein is expressed in 70-80% of human breast. Immunohistochemistry is the current method of choice for ER assessment, and its predictive value has been shown to be superior to that of biochemically based assays. Although accurate ER protein assessment is critical for optimal treatment of patients with breast cancer, studies have demonstrated inter-laboratory variability in ER detection. False-negative results for tumors with low ER protein levels have been a subject of recent concern. Lack of standardization for immunohistochemistry between laboratories is thought to be the major reason for testing errors, although variability in scoring methods and reporting practices, which can affect results, also plays a role. In this article, we review studies addressing interlaboratory variability and recommend optimal testing techniques and reporting procedures for ER testing, with the goal of increasing interlaboratory standardization for ER analysis by immunohistochemistry. We additionally highlight recent biologic, molecular, and gene expression profiling data related to ER in breast cancer.