Coexpression of Estrogen Receptor a and b: Poor Prognostic Factors in Human Breast Cancer?

The cloning of a second estrogen receptor (ER), ERb, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n 5 23) and malignant (n 5 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ERb predominated, with 22% of samples exclusively expressing ERb; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ERa, either alone or in combination with ERb. Interestingly, those tumors that coexpressed ERa and ERb were node positive (P 5 0.02; Fisher’s exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ERb in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ERb may be a useful prognostic factor in patients with breast cancer.