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Inhibition of Estrogen Receptor Action by a Naturally Occurring Variant in Human Breast Tumors¹

University of Texas Health Science Center, Department of Medical Oncology, San Antonio, Texas 78284-7884 [S. A. W. F, S. D. F., D. C. A., R. M. E., W. L. M.]; Baylor College of Medicine, Department of Cell Biology, Houston, Texas 77030 [Z. N., D. P. M., B. W. O.]; and Ben May Laboratories, University of Chicago, Chicago, Illinois 60637 [G. L. G.]

It is fairly well accepted that the presence of estrogen receptor (ER) and progesterone receptor (PgR) identifies breast cancer patients with a lower risk of relapse and better overall survival. But patients with discordant receptors, the ER⁺/PgR^- phenotype, are often intermediate in clinical response. We focused upon this group of patients and have identified a truncated ER which is abundant in some ER⁺/PgR^- breast tumors and which inhibits the binding of wild-type ER to its cognate response element. This variant interferes in a dominant negative manner with wild-type ER function and may represent a mechanism for modulation of estrogen responsiveness.

¹ Supported by NIH Grants CA52351-01 (S. A. W. F.) and CA30195 (W. L. M.).

² To whom requests for reprints should be addressed, at University of Texas Health Science Center, Division of Medical Oncology, 7703 Floyd Curl Drive, San Antonio, TX 78284-7884.

Received 10/17/91. Accepted 11/19/91.

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