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Estrogen Receptor Mutations in Human Disease

Breast Center, Baylor College of Medicine, Houston, Texas 77030

Correspondence: Address all correspondence and requests for reprints to: Suzanne A. W. Fuqua, Ph.D., Breast Center, Baylor College of Medicine, One Baylor Plaza, Mailstop 600, Houston, Texas 77030. E-mail: suzannef{at}breastcenter.tmc.edu

As early as the 1800s, the actions of estrogen have been implicated in the development and progression of breast cancer. The estrogen receptor (ER) was identified in the late 1950s and purified a few years later. However, it was not until the 1980s that the first ER was molecularly cloned, and in the mid 1990s, a second ER was cloned. These two related receptors are now called ER and ERß, respectively. Since their discovery, much research has focused on identifying alterations within the coding sequence of these receptors in clinical samples. As a result, a large number of naturally occurring splice variants of both ER and ERß have been identified in normal epithelium and diseased or cancerous tissues. In contrast, only a few point mutations have been identified in human patient samples from a variety of disease states, including breast cancer, endometrial cancer, and psychiatric diseases. To elucidate the mechanism of action for these variant isoforms or mutant receptors, experimental mutagenesis has been used to analyze the function of distinct amino acid residues in the ERs. This review will focus on ER and ERß alterations in breast cancer.

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