The expression of ERβcx in human breast cancer and the relationship to endocrine therapy and survival

Purpose: Estrogen receptor (ER) alpha-positive breast cancer is often treated with endocrine therapy using either antiestrogens or aromatase inhibitors. However, 30% of patients who receive endocrine therapy will derive no benefit from such treatments and may indeed suffer adverse effects. Currently, there are no ways to predict response to such treatments. ERbetacx, a variant of ERbeta, has a dominant-negative effect over ERalpha, and its expression thought to modulate response to endocrine treatment may represent a predictor of response to endocrine therapy. Experimental Design: We investigated the expression of the ERbetacx in 82 frozen breast samples (8 benign, 1 ductal carcinoma in situ, and 73 malignant) by Western blot analysis. The relationship between the expression of ERbetacx variants with prognosis and outcome of endocrine therapy was examined. Results: There was a statistically significant association between the presence of ERbetacx and the response to endocrine therapy (Fisher's exact test, P = 0.04). We also examined the influence of the ERbetacx status of a tumor on time to progression and death. There was a relationship between the presence of ERbetacx and survival, with patients whose tumors express ERbetacx having a longer survival rate (P = 0.05). Cell-type specificity of expression was assessed by immunohistochemistry on a selection of histological samples. Conclusions: On the basis of this small group of patients, we conclude that the expression of ERbetacx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.