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The Expression of ERßcx in Human Breast Cancer and the Relationship to Endocrine Therapy and Survival

¹ Department of Cancer Medicine, Cancer Cell Biology Group, Cancer Research UK Laboratories, Imperial College-London, Hammersmith Hospital, London, United Kingdom; ² Department of Medical Oncology, St. George’s Hospital, London, United Kingdom; ³ Department of Histopathology, Imperial College Faculty of Medicine and Charing Cross Hospital, London, United Kingdom; ⁴ Department of Social Science and Medicine, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, London, United Kingdom; and ⁵ Department of Medical Nutrition and Biosciences, Karolinska Institute, Huddinge, Sweden

Purpose: Estrogen receptor (ER) -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. ERßcx, a variant of ERß, has a dominant-negative effect over ER, 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 ERßcx 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 ERßcx variants with prognosis and outcome of endocrine therapy was examined.

Results: There was a statistically significant association between the presence of ERßcx and the response to endocrine therapy (Fisher’s exact test, P = 0.04). We also examined the influence of the ERßcx status of a tumor on time to progression and death. There was a relationship between the presence of ERßcx and survival, with patients whose tumors express ERßcx 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 ERßcx correlated with favorable response to endocrine therapy. A larger study involving the staining of archival material is currently underway to confirm these preliminary results.

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